Challenges

Grand Challenges

<h2>THE OPPORTUNITY</h2>
Embracing the tradition of microbial fermentation to transform locally available foods into naturally vitamin-fortified, toxin-free, flavorful, and shelf-stable products could empower local communities to mitigate the impact of COVID-19 on supply chain/food security and improve the health and nutrition of mothers and children in the most vulnerable settings. Historical advances in food processing have largely employed strategies that involve supplementation with micronutrients and additives to improve nutritional content and stability, but these approaches require highly centralized supply chains.<a href="#_edn1" name="_ednref1" title="" id="_ednref1">1</a> In addition, chemical additives for preservation, flavor and texture purposes may have unintended consequences of contributing to compromised gut health and increased prevalence of metabolic disease (hypertension, diabetes, obesity).<a href="#_edn2" name="_ednref2" title="" id="_ednref2">2</a>
Fermentation is an ancient practice through which locally-sourced food substrates can be transformed naturally by environmentally occurring microbes. These processes are thought to be intricately intertwined with human biology, and it is hypothesized that our primate ancestors adapted to natural fermentation processes millions of years ago.<a href="#_edn3" name="_ednref3" title="" id="_ednref3">3</a> While many fermented foods (e.g., yogurt, cheese, coffee and alcohol) remain popular, certain types of fermentation are a dwindling art in many settings, representing a loss of cultural heritage and a natural way to improve the qualities of foods across several distinct axes<a href="#_edn4" name="_ednref4" title="" id="_ednref4">4</a>:
<ul><li>Improve macro- and micro-nutrient quality and bioavailability (e.g., B vitamins)<a href="#_edn5" name="_ednref5" title="" id="_ednref5">5</a></li>
<li>Remove anti-nutrients (mycotoxins; phytates, which decrease iron availability)<a href="#_edn6" name="_ednref6" title="" id="_ednref6">6</a></li>
<li>Transform taste, flavor and texture<a href="#_edn7" name="_ednref7" title="" id="_ednref7">7</a></li>
<li>Improve the preservation and stability of foods by excluding pathogens (through lowering pH, bacteriocin production, removing simple sugars)<a href="#_edn8" name="_ednref8" title="" id="_ednref8">8</a></li>
</ul>Historical approaches of macronutrient supplementation and micronutrient fortification have been the basis for transformative global health nutrition interventions, ultimately saving millions of lives each year.<a href="#_edn9" name="_ednref9" title="" id="_ednref9">9</a> These approaches have also focused on pediatric populations, although recent work suggests that solutions targeting maternal nutrition may be even more impactful on pediatric health and have the important benefit of also improving maternal health.<a href="#_edn10" name="_ednref10" title="" id="_ednref10">10</a> Given limited access of nutritional interventions by the populations in greatest need<a href="#_edn11" name="_ednref11" title="" id="_ednref11">11</a> and formulations that are not optimized for gut and metabolic health,<a href="#_edn12" name="_ednref12" title="" id="_ednref12">12</a> malnutrition remains one of the most significant global health problems facing society today.
COVID-19, with disruption of supply chains and a predilection for individuals with metabolic diseases, has served to increase the urgency for identifying locally-sourceable health-promoting maternal nutrition solutions that treat undernutrition without increasing the risk of obesity, diabetes, and hypertension. Ironically, it may be that these new solutions already exist in the form of ancient traditions reevaluated and revalued through a next-generation and evidence-based lens.
<h2>THE CHALLENGE</h2>
Beyond many of the well-known examples of microbial fermentation, the vast majority of fermentation processes around the world remain uncharacterized and their potential human health benefits are unknown. These ancient practices may hold the key to impactful and locally targeted nutritional interventions that combine tradition and science to tackle malnutrition. Rigorous scientific evaluation has been limited and characterization to understand potential benefits could be pursued to validate and underscore the importance of preserving this cultural heritage.
What we are looking for
This call seeks to fund pilot studies that investigate the biological effect of traditional locally fermented foods on key microbiome, gut, and health biomarkers in local populations. The goal is to provide investigators in Sub-Saharan Africa and South Asia with the resources to build local capacity to investigate fermented foods as novel maternal nutrition interventions. In particular, sequencing technology – a transformative tool that has enabled in-depth investigation of microbial communities – will be provided to all investigators to democratize the ability to investigate foods and health effects, and build local capacity. Ultimately, the goal is to empower local communities to develop geography and culture specific interventions powered by fermentation, in country.
Proposals should specifically address the following core elements, but investigators are welcome to propose creative strategies and designs to accomplish the core goals of this call and account for local cultural traditions. In addition, it is expected that study design will be refined after award through a collaborative forum invovling other awardees and the foundation:
<ul><li>Identification of a local (geographic/cultural) fermented food for study
<ul><li>Many foods may not be colloquially considered to be fermented, but any process that incorporates biotransformation by microbes is acceptable</li>
<li>Living microbes were actively employed as a part of the fermentation process and final product consumed retains live organisms</li>
<li>Fermentation may be driven by known organisms, e.g. bacterial Lactobacillus sp., fungal Aspergillus sp., or less studied food-borne organisms</li>
<li>Must be plant-based (e.g., grain or staple crop). Plant-based fermented foods are a requirement due to lower cost of goods for scalability compared to animal-based foods</li>
<li>Food with a cultural precedent in maternal nutrition are of high interest</li>
<li>The food being investigated must be produced in compliance under all relevant local food manufacturing regulations and modern food safety practices</li>
</ul></li>
<li>Pilot study design for longitudinal intervention study for understanding the effect of the fermented food in a naïve (no, or limited, fermented food consumption) population
<ul><li>The target population should be women of reproductive age, and a naive population not currently consuming or with limited consumption of the target fermented food to better understanding the biological effects of the food itself. Different subpopulations (urban vs. rural, various cultural groups, different sub-geographies within a country, etc.) with lower consumption of the target fermented food could be specifically targeted. If populations traditionally consuming fermented foods are considered, it would be important to undertake a baseline to understand the additive effect after consumption of "target foods".</li>
<li>Longitudinal intervention studies are recommended, with small cohort sizes (20-30 participants) and sustained exposure to the fermented food (e.g., at least daily &gt;5 days) but ultimately the study design should be motivated by the end goal of characterizing the effects of the food on maternal nutrition through host (blood and fecal) and gut microbiome biomarkers.</li>
<li>A template dietary questionnaire will be provided and can be customized to local foods and traditions</li>
<li>Existing infrastructure that may improve ability to execute on the proposed study can and should be highlighted</li>
</ul></li>
<li>Biological sample biobanking and characterization before and after food intervention
<ul><li>Fermented foods themselves (metagenomic analysis of fungal [ITS] and bacterial [16S] constituents), potentially across distinct batches and preparation methods</li>
<li>Serial fecal samples from participants (metagenomic analysis; lipocalin-2, myeloperoxidase, and calprotectin of particular interest)</li>
<li>Serial serum/blood samples from participants (Iron studies, B-vitamin analysis; lipocalin-2, IL-6 and CRP are of particular interest given the association of inflammation biomarkers with maternal nutrition and birth outcomes) <a href="#_edn13" name="_ednref13" title="" id="_ednref13">13</a></li>
<li>Other characterization approaches of food (including effects of fermentation on the nutritional profile) or biological samples using conventional or existing techniques</li>
<li>Proposals should specifically address existing laboratory infrastructure and capacity for integrating next generation sequencing into existing laboratory workflows (e.g. nucleic acid extraction, PCR, etc.)</li>
</ul></li>
</ul>As a part of this 18 month Grand Challenges award, sequencing platforms (funded with up to USD $40K for sequencing technology out of this USD $200K award) and training will be provided to investigators to enable local sequence-based characterization of the fermented foods and microbiome effects. The output of this study will be pilot data evaluating the biological effect of traditional fermented foods on gut, microbiome and health axes in local populations. Any additional points on the sustainability of the intervention and the empowerment of local champions to continue the work, integrating with state and national level Maternal, Infant and Young Child Nutrition (MIYCN) programs would also be welcome.
What we will not consider funding 
<ul><li>Investigators and institutions not located in Sub-Saharan Africa or South Asia</li>
<li>Investigators not studying local foods (specific to the culture or geography)</li>
<li>Investigators not investigating local populations</li>
<li>Proposals that do not contain a human interventional study targeted towards women of reproductive age. No studies on child populations will be funded.</li>
<li>Proposals not addressing all the stated study design criteria above</li>
<li>Proposals that do not demonstrate a capacity to perform the research proposed; investigators should describe capacity for human studies, sample collection, processing and storage, including but not limited to:
<ul><li>Relevant approvals from local authorities/institutions/Government on the research methodology and sharing of data among collaborators, eventually for global access</li>
<li>Data analysis and adherence to relevant local laws/ policies pertaining to data sharing, hosting and data protection.</li>
<li>Secure handling of personally identifiable information data and research results</li>
<li>Institutional Review Boards or equivalent human study regulation strategy</li>
<li>Sample collection capacity/protocols and capacity for sample storage</li>
<li>Ability to perform human biological sample characterization as proposed</li>
</ul></li>
</ul>___________________________________
References
<a href="#_ednref1" name="_edn1" title="" id="_edn1">[1]</a> <a href="https://www.fao.org/3/a-i3953e.pdf" target="_blank">https://www.fao.org/3/a-i3953e.pdf</a>
<a href="#_ednref2" name="_edn2" title="" id="_edn2">[2]</a> <a href="https://www.nature.com/articles/nature14232/" target="_blank">https://www.nature.com/articles/nature14232/</a>
<a href="#_ednref3" name="_edn3" title="" id="_edn3">[3]</a> <a href="https://www.pnas.org/content/112/2/458" target="_blank">https://www.pnas.org/content/112/2/458</a>
<a href="#_ednref4" name="_edn4" title="" id="_edn4">[4]</a> <a href="https://www.sciencedirect.com/science/article/pii/S0958166919300990" target="_blank">https://www.sciencedirect.com/science/article/pii/S0958166919300990</a>
<a href="#_ednref5" name="_edn5" title="" id="_edn5">[5]</a> <a href="https://academic.oup.com/advances/article/4/4/463/4259633" target="_blank">https://academic.oup.com/advances/article/4/4/463/4259633</a>
<a href="#_ednref6" name="_edn6" title="" id="_edn6">[6]</a> <a href="https://www.sciencedirect.com/science/article/abs/pii/0963996994900965" target="_blank">https://www.sciencedirect.com/science/article/abs/pii/0963996994900965</a>
<a href="#_ednref7" name="_edn7" title="" id="_edn7">[7]</a> <a href="https://ifst.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2621.1999.00245.x" target="_blank">https://ifst.onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2621.1999.00245.x</a>
<a href="#_ednref8" name="_edn8" title="" id="_edn8">[8]</a> <a href="https://www.karger.com/Article/Abstract/104752" target="_blank">https://www.karger.com/Article/Abstract/104752</a>
<a href="#_ednref9" name="_edn9" title="" id="_edn9">[9]</a> <a href="https://link.springer.com/article/10.1186/2046-4053-2-67" target="_blank">https://link.springer.com/article/10.1186/2046-4053-2-67</a>
<a href="#_ednref10" name="_edn10" title="" id="_edn10">[10]</a> <a href="https://academic.oup.com/ajcn/article/109/2/457/5307124" target="_blank">https://academic.oup.com/ajcn/article/109/2/457/5307124</a>
<a href="#_ednref11" name="_edn11" title="" id="_edn11">[11]</a> <a href="https://www.who.int/maternal_child_adolescent/topics/child/malnutrition/en/" target="_blank">https://www.who.int/maternal_child_adolescent/topics/child/malnutrition/en/</a>
<a href="#_ednref12" name="_edn12" title="" id="_edn12">[12]</a> <a href="https://science.sciencemag.org/content/365/6449/eaau4732" target="_blank">https://science.sciencemag.org/content/365/6449/eaau4732</a>
<a href="#_ednref13" name="_edn13" title="" id="_edn13">[13]</a> <a href="https://pubmed.ncbi.nlm.nih.gov/28274163/" target="_blank">https://pubmed.ncbi.nlm.nih.gov/28274163/</a>

Grand Challenges seeks pilot studies that investigate the biological effect of traditional locally fermented foods on key microbiome, gut, and health biomarkers in local populations. The goal is to provide investigators in Sub-Saharan Africa and South Asia with the resources to build local capacity to investigate fermented foods as novel maternal nutrition interventions.

Integrating Tradition and Technology for Fermented Foods for Maternal Nutrition

Note: Please see the request for proposals document with additional background as a PDF file on the right.
<h2>Summary</h2>
Smart Farming Innovations for Small-Scale Producers Request for Proposals (RFP) seeks Smart Farming solutions that leverage digital technology innovations that have the potential to drive positive impact for smallscale producer (SSP) entrepreneurs delivered through bundled farmer services and enabled by scalable digital and data platforms (<a href="#Fig1" id="_Fig1">Figure 1</a>). Solutions should address one or more challenges faced by smallscale crop and livestock producers in one or more areas of agricultural advisory, farm management decision support, input supply, finance, insurance, market access and linkages. Solutions should use human-centered design to elucidate the barriers that prevent SSPs from improving productivity, profitability and income – then propose Smart Farming solutions that can help elevate smallscale production entrepreneurs. Some of the fundamental challenges to address include: 1) low productivity driven by lack of access to information and services; climate change, weather variability and pest and disease outbreaks; 2) lack of access to tailored financial and insurance products, and 3) lack of access to and choice of market and offtake options. Additionally, solutions will need to consider barriers to adoption of digital farmer services, such as low language and digital literacy, the high relative cost of services and devices and, in particular, gender gaps and other potential downsides of digital solutions (e.g. the growing digital divide).
<img alt="" height="406" src="https://stage-drupal.grandchallenges.org/sites/default/files/images/farming-digital-technologies-diagram.jpg" width="414" />
<a href="#_Fig1" id="Fig1">Figure 1</a>. Smart Farming Innovations for SSPs
Awards: There are two grant types – Seed Grants and Scale-Up Grants – each with its own requirements. Applicants can only apply for one of these grant types must select which level for which they are applying (proposal should not be submitted for both grant types).
Seed Grants – Up to USD 250,000 to be implemented up to 12 months. Seed Grants are proposals for Smart Farming solutions that can demonstrate potential in meeting the following criteria:
<ul><li>Leveraging digital technology innovations with the potential to scale, for example, utilizing a proven technology that has been applied in agriculture in another geography; transferring a technology from another sector such as health, infrastructure or finance; sourcing an entirely new technology;</li>
<li>Show potential to improve SSP incomes, productivity and ability to adapt to climate change;</li>
<li>Address barriers to scaled adoption of digital services, such as access, affordability and language and digital literacy. This includes addressing women's access to digital services and closing the digital divide between those who have access and marginalized populations who do not;</li>
<li>Have the potential to be bundled with multiple farmer-facing services into an integrated solution;</li>
<li>Are enabled by robust digital and data technology platforms and services;</li>
<li>Provide fit-for-purpose solutions (e.g. developed using human-centered design) for SSP enterprises who seek to sell a portion of production to markets;</li>
<li>Show potential to be scaled using a sustainable business model and are affordable and able to provide positive return on investment at a smallholder farm level through successful pilots, scaling partners, or higher volume production driving down prices.</li>
</ul>Scale-Up Grants – Up to USD 1,500,000 to be implemented up to 24 months. Scale-Up Grants are proposals with demonstrated ability and sufficient evidence to have positive impact. In addition to the criteria listed above for Seed Grants, Scale-Up Grants must also:
<ul><li>Leverage digital technology innovations with demonstrated readiness to scale and proven ability to bundle with other services;</li>
<li>Meet all criteria regarding technology innovations, scalable platforms, and sustainable bundled service delivery models;</li>
<li>Demonstrate that additional funding will enable value capture by SSPs or other value chain actors and sustainable and viable service delivery models over the long term.</li>
<li>Please upload a separate document – 1 additional page maximum – that describes your partner consortium in more detail, including the various partners' capabilities, and additional evidence of value add, income, productivity, women's empowerment and long-term sustainability of the solution.</li>
</ul>Consortiums: To increase the probability that projects funded through this RFP will continue after the initial project completion and evolve into a continuing global public good or sustained solution, applicants are encouraged to consider of a range of partners to form a consortium. This investment will prioritize those who partner with organizations interested in Smart Farming in low- and middle-income countries (LMICs) as long-term opportunities. There are several types of organizations we envisage being part of consortia submitting proposals: Enterprise Technology Platforms (Big-Tech), Enterprise Agriculture (Big-Ag), Ag-Tech Startups (Ag-Tech + Farm-Tech), Research Organizations (R&amp;D), national and international NGOs and farmer-based organizations (Implementors), Government and International Organizations.
Geographies: While we primarily seek solutions applicable to the LMICs listed below and favor those forming local partnerships. Other geographies will be considered if a strong case is made for doing so.
<ul><li>Africa: Kenya, Uganda, Ethiopia, Tanzania, Rwanda, Ghana, Senegal, Mali, Burkina Faso, Malawi, Zambia, Mozambique</li>
<li>Asia: India (Bihar, Odisha, Uttar Pradesh, Andhra Pradesh), Bangladesh</li>
</ul>

Grand Challenges seeks innovative digital solutions with potential to scale and integrate with bundled farmer services. Solutions should address one or more challenges facing small scale crop and livestock producer entrepreneurs in the areas of agricultural advisory, input supply, finance, insurance, market access, and decision support tools.

Smart Farming Innovations for Small-Scale Producers

Balance the Equation is the first-ever Grand Challenge focused on U.S. education. The Bill &amp; Melinda Gates Foundation is seeking to disrupt the deeply imbalanced system against this generation – and previous generations – of Black, Latino, English Learners (ELs), and students experiencing poverty in the United States, who we will refer to as priority students, as it relates to their Algebra 1 experience in 7th, 8th, or 9th grade, in-class or online.

Balance the Equation - A Grand Challenge for Algebra 1

<h2>BACKGROUND</h2>

Cesarean section (CS) is a life-saving procedure for mother and newborn. However, too often c-section is not available, is provided without adequate quality, or is provided when not medically indicated - all dimensions that lead to maternal and newborn mortality and morbidity. We see an opportunity to nurture the field to identify and demonstrate feasibility of interventions to address challenges related to safe, timely, and appropriate cesarean section in low and middle income countries.

<h2>THE CHALLENGE</h2>

We invite proposals for interventions to address the following challenges related to the cesarean section:

<ol>
	<li>Increasing access to cesarean section where it is currently inadequate</li>
	<li>Increasing quality and safety of cesarean section to reduce iatrogenic harm to both mothers and newborns</li>
	<li>Reducing rates of non-medically indicated cesarean section.</li>
</ol>

Interventions addressing more than one challenge (e.g. quality and access) are encouraged. In some geographies all three of these challenges exist simultaneously, at different times for different populations; in other geographies only one or two of these challenges predominate. Applications should clearly state which of these three challenges is being targeted and provide clear rationale for why the intervention is likely to address the challenge. We are particularly interested in geographies with high fertility and weak health systems that will face challenges to ensure the provision of safe c-sections can keep pace with medical need, and we will thus consider applications proposing activities to be implemented in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).

Grant Funding Levels

We seek to make Seed Grants to generate proof of concept of novel interventions together with Validation Grants to generate further evidence of feasibility at a larger scale for existing interventions.

<ul>
	<li>Seed Grants of $100K for up to 24 months: These grants are intended to provide proof of concept of an intervention that is entirely novel at small scale (e.g., single facility or district). Applicants should conduct a literature review to verify that the proposed intervention has no documented evidence; documentation of the methods and outcomes of this review must be provided in the application. These grants should demonstrate the feasibility of a novel intervention and its impact on one or more of the c-section challenges identified in this call for applications.</li>
	<li>Validation Grants of $300K for up to 24 months: These grants are intended to demonstrate the feasibility of a single intervention or a combination of interventions at the scalable unit <a href="#_ftn1" id="_ftnref1">[1]</a> of a health system. Validation grants must replicate, confirm or more rigorously test one intervention - or multiple interventions - that have previously demonstrated proof of concept at a smaller scale. Given the complexity of the problem, we acknowledge that multi-component interventions are required, and we eoncourage applications exploring these.</li>
</ul>

What We Are Looking For:

All applications should:

<ul>
	<li>Focus on health service or delivery innovation. This call for applications excludes development of new medical devices and non-interventional analysis of data</li>
	<li>Describe how the intervention will be tailored to the epidemiology and health system where it will be implemented</li>
	<li>Ensure that women and newborns receive care that respects and preserves their dignity, including informed consent<a href="#_ftn2" id="_ftnref2" name="_ftnref2">[2]</a></li>
	<li>Include participation from institutions based in South Asia and sub-Saharan Africa; applications led by institutions from these geographies are encouraged</li>
	<li>Propose interventions that align with the attributes of scalable health innovations<a href="#_ftn3" id="_ftnref3" name="_ftnref3">[3]</a></li>
	<li>Report impact on c-section rates disaggregated by Robson classification<a href="#_ftn4" id="_ftnref4" name="_ftnref4">[4]</a>, and safety with indicators such as case fatality rates and rates of post-operative complication</li>
	<li>Propose activities to be implemented in a country in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).</li>
</ul>

A few of the many options we will consider include (but are not limited to): clinical team huddles for improving quality of CS; interventions to improve immediate breastfeeding and bonding among mother-infant pairs after CS; interventions to improve communication between patient and care team; restructuring labor wards to facilitate latent phase labor management; adjustments to financial incentives related to CS; policy and liability reform.

We will not consider funding for approaches that have been widely used and evaluated in LMIC settings to scale up access to cesarean section (e.g., task shifting); activities to improve quality of care that already have extensive evidence of effectiveness; emergency transport interventions; mass media campaigns; or development of new tools for surgery, anesthesia, or patient monitoring.

Collaboration

This request for proposals seeks to create a consortium of individually funded projects that will benefit from sharing information between projects. We expect that such sharing will help to ensure that the goals of the innovative approaches in individual projects are ultimately integrated with each other, thereby increasing the chances that the programs will be greater than the sum of their parts. Furthermore, we expect that sharing experimental methods, data, and resources will ultimately improve the ability to compare and validate local research findings and to develop interventions and products. We expect to bring together all grantees after 18-24 months to share what they have learned in their work and to discuss how to accelerate progress with these lessons.

<drupal-media data-align="center" data-entity-type="media" data-entity-uuid="6e3e1e63-035c-4e42-93c0-8ddc90679019"></drupal-media>

Figure 1. Framework for considering cesarean section

________________________________

<a href="#_ftnref1" id="_ftn1">[1]</a><a href="https://implementationscience.biomedcentral.com/articles/10.1186/s13012-016-0374-x" target="_blank">Barker P, Reid A, Schall M. A Framework for scaling up health interventions: lessons learned from large scale improvement initiatives in Africa. Implementation Science. 2016</a>.

<a href="#_ftnref2" name="_ftn2" title="">[2]</a><a href="https://www.who.int/maternal_child_adolescent/documents/improving-maternal-newborn-care-quality/en/" target="_blank">WHO. Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. 2016.</a>

<a href="#_ftnref3" name="_ftn3" title="">[3]</a><a href="https://www.sciencedirect.com/science/article/pii/S0277953614006133" target="_blank">Spicer et al. "Scaling-up is a craft not a science: Catalysing scale-up of health innovations…" Social Science and Medicine. 2014"</a>

<a href="#_ftnref4" name="_ftn4" title="">[4]</a><a href="https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/robson-classification/en/" target="_blank">WHO. Robson Classification: Implementation Manual. 2017</a>

<h2>BACKGROUND</h2>
Cesarean section (CS) is a life-saving procedure for mother and newborn. However, too often c-section is not available, is provided without adequate quality, or is provided when not medically indicated - all dimensions that lead to maternal and newborn mortality and morbidity. We see an opportunity to nurture the field to identify and demonstrate feasibility of interventions to address challenges related to safe, timely, and appropriate cesarean section in low and middle income countries.
<h2>THE CHALLENGE</h2>
We invite proposals for interventions to address the following challenges related to the cesarean section:
<ol><li>Increasing access to cesarean section where it is currently inadequate</li>
<li>Increasing quality and safety of cesarean section to reduce iatrogenic harm to both mothers and newborns</li>
<li>Reducing rates of non-medically indicated cesarean section.</li>
</ol>Interventions addressing more than one challenge (e.g. quality and access) are encouraged. In some geographies all three of these challenges exist simultaneously, at different times for different populations; in other geographies only one or two of these challenges predominate. Applications should clearly state which of these three challenges is being targeted and provide clear rationale for why the intervention is likely to address the challenge. We are particularly interested in geographies with high fertility and weak health systems that will face challenges to ensure the provision of safe c-sections can keep pace with medical need, and we will thus consider applications proposing activities to be implemented in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).
Grant Funding Levels
We seek to make Seed Grants to generate proof of concept of novel interventions together with Validation Grants to generate further evidence of feasibility at a larger scale for existing interventions.
<ul><li>Seed Grants of $100K for up to 24 months: These grants are intended to provide proof of concept of an intervention that is entirely novel at small scale (e.g., single facility or district). Applicants should conduct a literature review to verify that the proposed intervention has no documented evidence; documentation of the methods and outcomes of this review must be provided in the application. These grants should demonstrate the feasibility of a novel intervention and its impact on one or more of the c-section challenges identified in this call for applications.</li>
<li>Validation Grants of $300K for up to 24 months: These grants are intended to demonstrate the feasibility of a single intervention or a combination of interventions at the scalable unit<a href="#Note1">1</a> of a health system. Validation grants must replicate, confirm or more rigorously test one intervention - or multiple interventions - that have previously demonstrated proof of concept at a smaller scale. Given the complexity of the problem, we acknowledge that multi-component interventions are required, and we eoncourage applications exploring these.</li>
</ul>What We Are Looking For:
All applications should:
<ul><li>Focus on health service or delivery innovation. This call for applications excludes development of new medical devices and non-interventional analysis of data</li>
<li>Describe how the intervention will be tailored to the epidemiology and health system where it will be implemented</li>
<li>Ensure that women and newborns receive care that respects and preserves their dignity, including informed consent<a href="#Note2">2</a></li>
<li>Include participation from institutions based in South Asia and sub-Saharan Africa; applications led by institutions from these geographies are encouraged</li>
<li>Propose interventions that align with the attributes of scalable health innovations<a href="#Note3">3</a></li>
<li>Report impact on c-section rates disaggregated by Robson classification<a href="#Note4">4</a>, and safety with indicators such as case fatality rates and rates of post-operative complication</li>
<li>Propose activities to be implemented in a country in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).</li>
</ul>A few of the many options we will consider include (but are not limited to): clinical team huddles for improving quality of CS; interventions to improve immediate breastfeeding and bonding among mother-infant pairs after CS; interventions to improve communication between patient and care team; restructuring labor wards to facilitate latent phase labor management; adjustments to financial incentives related to CS; policy and liability reform.
We will not consider funding for approaches that have been widely used and evaluated in LMIC settings to scale up access to cesarean section (e.g., task shifting); activities to improve quality of care that already have extensive evidence of effectiveness; emergency transport interventions; mass media campaigns; or development of new tools for surgery, anesthesia, or patient monitoring.
Collaboration
This request for proposals seeks to create a consortium of individually funded projects that will benefit from sharing information between projects. We expect that such sharing will help to ensure that the goals of the innovative approaches in individual projects are ultimately integrated with each other, thereby increasing the chances that the programs will be greater than the sum of their parts. Furthermore, we expect that sharing experimental methods, data, and resources will ultimately improve the ability to compare and validate local research findings and to develop interventions and products. We expect to bring together all grantees after 18-24 months to share what they have learned in their work and to discuss how to accelerate progress with these lessons.
<a href="https://gcgh.grandchallenges.org/sites/default/files/C-Section_Chart_Square.jpg" target="_parent"><img alt="" src="https://gcgh.grandchallenges.org/sites/default/files/C-Section_Chart_Square.jpg" /></a> 
Figure 1. Framework for considering cesarean section
________________________________
<a name="#Note1" id="#Note1">1</a><a href="https://implementationscience.biomedcentral.com/articles/10.1186/s13012-016-0374-x" target="_blank">Barker P, Reid A, Schall M. A Framework for scaling up health interventions: lessons learned from large scale improvement initiatives in Africa. Implementation Science. 2016</a>.
<a name="#Note2" id="#Note2">2</a><a href="https://www.who.int/maternal_child_adolescent/documents/improving-maternal-newborn-care-quality/en/" target="_blank">WHO. Standards for Improving Quality of Maternal and Newborn Care in Health Facilities. 2016.</a>
<a name="#Note3" id="#Note3">3</a><a href="https://www.sciencedirect.com/science/article/pii/S0277953614006133" target="_blank">Spicer et al. "Scaling-up is a craft not a science: Catalysing scale-up of health innovations…" Social Science and Medicine. 2014"</a>
<a name="#Note4" id="#Note4">4</a><a href="https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/robson-classification/en/" target="_blank">WHO. Robson Classification: Implementation Manual. 2017</a>

Grand Challenges seeks ideas for interventions to address the following challenges related to cesarean section: 1) increasing access to cesarean section where it is currently inadequate, 2) increasing quality and safety of cesarean section to reduce iatrogenic harm to both mothers and newborns, 3) reducing rates of non-medically indicated cesarean section. Proposed activities should be implemented in Sub-Saharan Africa or South Asia (India, Pakistan, Bangladesh).

Improving Access to and Use of Safe and Appropriate Cesarean Section

"That's the idea behind Grand Challenges - to focus bright scientists on the problems of the poorest, take some risks, and deliver results." Bill Gates

"Family planning and access to contraception - including information, supplies, and services - is an issue that I am passionate about, and it has become one of my personal priorities at the foundation. 
I believe it's one of the most urgent issues of our time." Melinda Gates

<h2>Background</h2>

Family planning is one of the most cost-effective ways to reduce maternal, infant and child mortality and contributes to the empowerment of women and families, as well as the expansion of opportunities for economic development. In recent decades, there have been tremendous improvements in the reproductive health of women in low resource settings. Global efforts have substantially accelerated progress toward the goal of reaching 120 million additional users of contraception by 2020 in the world’s poorest countries, an achievement well worth celebrating. Nonetheless, it is estimated that over 214 million women in developing countries have an unmet need for modern contraception.

While current contraceptive methods for women include exceptionally safe and effective options, not all methods are suitable for or acceptable to all women at all stages of their reproductive lives, and concerns about undesirable side effects remain a significant barrier to greater uptake and continued use of existing methods. As a result, women who desire to avoid pregnancy often find themselves without viable options that meet their needs. In particular, changes in uterine bleeding patterns are associated with use of hormonal contraceptive methods and copper intrauterine devices and, combined with access challenges and social or religious norms related to contraceptive use or menstrual bleeding, contribute to high discontinuation rates for these methods (up to 40% in the first year of use). While the concept of developing a non-hormonal pharmaceutical contraceptive with an improved tolerability profile as a suitable alternative has been promoted through research efforts and publications, a focused discovery effort has not been systematically pursued.

<h2>THE CHALLENGE</h2>

The Bill &amp; Melinda Gates Foundation is committed to a long-term vision of expanding contraceptive options for the most vulnerable women in low-resource settings through development of new methods that better align with women’s preferences. Contraceptive product innovation will be required to achieve this goal. Specifically, the emphasis for this work is on developing safe and effective non-hormonal contraceptive agents with both improved overall tolerability and a side effect profile differentiated from hormonal methods. This emphasis is based on an understanding that overall tolerability of and side effects from hormonal methods present real and meaningful barriers to women realizing their reproductive intentions.

This vision demands establishment of a strong research foundation upon which to build a robust pipeline of product candidates, recognizing that the attrition rate of products in preclinical and clinical development will likely be substantial due to the high bar for safety and efficacy. In order to establish a set of critical reproductive biology and early stage discovery capabilities, insource novel ideas from other areas of science, and improve the knowledge base needed to support such an effort, the foundation is launching the "Accelerating Discovery for Non-Hormonal Contraceptives" Grand Challenge in 2020. The goal of this Grand Challenge is to identify new approaches and concepts directed at the characterization of novel contraceptive drug targets, the identification of active contraceptive compounds useful for target validation and proof-of-principle studies, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&amp;D.

The ultimate outcome driving the foundation’s investment in this area is the discovery new drug candidates that i) provide safe and effective contraception, ii) do not rely on systemic administration of reproductive steroid hormones or act through perturbation of sex steroid pathways, and iii) are suitable and appropriate for deployment in a low resource setting. The focus of this Grand Challenge is on broadly enhancing the research ecosystem for contraceptive discovery and advancing novel and bold ideas that can accelerate drug discovery in this field. We do not expect that novel contraceptive product candidates ready for entry into preclinical development will be identified in this early stage of funding. We anticipate, however, that projects funded through this Grand Challenge will identify new drug discovery approaches and technologies that have yet to be effectively applied to contraceptive R&amp;D. We expect to engage a broad range of expertise across disciplines in a collaborative and coordinated research program. It is anticipated, but not guaranteed, that success in these efforts would justify additional investment in a broader drug discovery effort by the Bill &amp; Melinda Gates Foundation, with the goal of developing innovative non-hormonal contraceptive methods to better serve the needs of women.

Approach

As approaches to discovery of new drugs for other indications have become increasingly sophisticated, these advances have not been applied to field of contraceptives. As a result, critical technical barriers continue to hamper progress and limit our ability to effectively identify novel contraceptive agents. These barriers include, but are not limited to:

<ul>
	<li>The inability to appropriately replicate in the laboratory a number of complex multi-cellular reproductive processes for the purposes of compound screening (e.g. ovulation);</li>
	<li>Poor understanding of contraceptive drug targets associated with key fertility pathways, and a lack of validated and scalable approaches to validate and assay potential targets;</li>
	<li>Lack of appropriate medium- to high-throughput phenotypic screening methodologies for identifying compounds capable of exerting a specific and potent contraceptive effect;</li>
	<li>Lack of appropriate in vitro and in vivo preclinical assays and biomarkers to assess i) the efficacy of agents targeting novel contraceptive mechanisms and ii) the potential side effects of novel agents.</li>
</ul>

It is our belief that these challenges can be addressed, and that doing so will create substantial new opportunities for contraceptive drug discovery. We seek to leverage advances in other areas of reproductive biology, both basic and applied, and emerging technologies in drug discovery to establish a suite of capabilities that can support a robust drug discovery program. It is not our intention to establish fully integrated end-to-end drug discovery capabilities with individual institutions through this program, but rather to fund a network of researchers, with each bringing a unique approach, and facilitate interactions between partners to maximize impact. Applicants should keep this in mind when articulating a project plan and focus on the key strengths that their expertise, approach, and technology can provide. Proposals should be aligned with one or more of the funding focus areas outlined below.

We are looking for proposals that:

<ul>
	<li>Engage scientists across a variety of disciplines, including those new to the field of contraceptive R&amp;D;</li>
	<li>Demonstrate innovative thinking by applying or incorporating concepts, methods or technologies not currently being used for contraceptive discovery;</li>
	<li>Present concepts and strategies that are "off the beaten track", significantly radical in conception, and daring in premise;</li>
</ul>

We will NOT consider funding for:

<ul>
	<li>Proposals focused on development of male contraceptives, including work on sperm-based approaches that could only feasibly be applied as vaginal methods;</li>
	<li>Proposals targeting the endometrium for the prevention on embryo implantation;</li>
	<li>Proposals on novel drug delivery systems for contraception;</li>
	<li>Discovery of adjunct or complementary molecules intended for co-delivery with hormonal contraceptive regimens;</li>
	<li>Basic studies of human reproductive biology without a clear connection to enabling non-hormonal contraceptive discovery;</li>
	<li>Pre-clinical or clinical development of advanced leads and candidates;</li>
	<li>Social science, marketing, or acceptability studies related to contraceptive use and uptake.</li>
</ul>

Awardees through this Grand Challenge may have the opportunity to access other Gates Foundation-funded resources, technology platforms, and grantee networks to help support their projects, facilitated by their Gates Foundation Program Officer. Applicants should, as completely as possible, describe what the proposed project will deliver within the scope of the application and the potential path forward, even if that encompasses activities that are beyond the scope of the current funding opportunity. Applicants invited to submit full proposals following LOI review (see the Review Process as detailed in the Rules and Guidelines) should expect to include critical milestones and relevant go/no-go decisions for the proposed project.

Funding Focus Areas:

<ol>
	<li>Biological Assay Development

	Many aspects of female reproduction remain challenging to replicate or model in a tractable, physiologically relevant, and highly reproducible fashion, but such tools and models will be fundamentally important to identifying and profiling contraceptive drug targets and contraceptive compounds. A better toolset of in vitro assays is needed that can recapitulate oocyte and follicle development, follicle selection, follicular rupture/ovulation, corpus luteum formation, cumulus-oocyte complex dynamics, and fertilization, including peri-fertilization events. New models should focus on assay tractability as well as establishing physiological relevance and modeling closely relevant features of the in vivo environment. Applicants seeking to develop such systems should clearly describe the planned approach and how this would improve upon existing methods. Including approaches to validate with human samples or human genetics/genomic information would be viewed favorably. Proposals should include a discussion on how assays will be standardized, validated, and scaled, including where possible the use of genetic or chemical probes as positive controls to demonstrate biologically relevant outcomes following assay perturbation.
	</li>
	<li>Drug Target Identification and Validation
	In the past two decades, target-based drug discovery approaches have become increasingly sophisticated and powerful, but further and complementary approaches are needed to sustain a pipeline of potential drug targets and enhance our understanding of target biology. Emphasis will be placed on unbiased approaches to identify potential contraceptive drug targets. These may include (but are not limited to):

	<ul>
		<li>RNAi- or CRISPR-based methods utilizing a robust and relevant biological assay,</li>
		<li>chemical genomics or proteomics linking probe compound activity to specific drug targets or pathways,</li>
		<li>analyses of human infertility as a pathway to identify relevant drug targets, or</li>
		<li>artificial intelligence-enabled approaches to target identification.</li>
	</ul>

	 
	Target characterization and validation efforts should focus on the determination of whether any particular gene that is critical for a reproductive process is vulnerable to inhibition by a small molecule inhibitor (using, for example, tunable knockdown or inducible degradation techniques), can likely be safely modulated by such an inhibitor (including assessment of roles in somatic tissue and activity of closely related homologs), and is likely to provide the desired contraceptive effect at realistic levels of inhibition (as opposed to complete loss-of-function). Applicants should clearly describe the critical assays, methods, or approaches they are proposing to underpin this work, and describe how such approaches will yield compelling and relevant data that could be used to support entry of identified targets into target-based drug discovery activities.
	</li>
	<li>Chemical genomics, probe generation, pilot screening
	The availability of active compounds that interfere with key steps in fertility would open up many avenues for further biological exploration and target validation, but methods for screening small compound libraries for chemical probe discovery are currently limited. Applications will be considered that propose small pilot-scale screening in complex systems for the purposes of identifying active compounds interfering with key reproductive functions. Applicants must detail how screening systems will be developed, tested, and validated in a format suitable for testing compounds, and should detail the type and source of chemical libraries that would be utilized. Biologically-informed hypotheses may be proposed to select mechanism- or target class-focused libraries as a starting point. We will not consider applications for screening of a single proposed target, but mechanism-focused approaches that interrogate multiple targets involved in a key reproductive process would be considered. Applicants must then describe an approach to deduce the specific targets of compounds identified in cell-based screens and demonstrate concordance between target-based activity and functional activity in validated in vitro systems.
	</li>
	<li>Contraceptive Antibodies
	While the cost and practicality of antibody-based therapeutics has historically been a challenge, particularly for application in a low resource setting, new advances in antibody half-life extension and cost-effective production open up the possibility that antibodies may be a more tractable option in the future, particularly if used in an "on demand" contraceptive modality. Moreover, this may allow consideration of targets that would otherwise not be amenable to small molecule inhibitors and may provide an enhanced safety window. Applications focused on contraceptive antibodies should clearly articulate the data supporting the validation of the proposed antigen target, the methods to be used for antibody identification, and the assays to be used relevant to determination of antibody function.

	(Note: the foundation is not accepting applications based on contraceptive immunization as an intervention modality, though such approaches could be applied experimentally for target validation.)
	</li>
	<li>Translational Science/Preclinical Evaluation Tools
	In addition to target and hit discovery activities, downstream aspects of drug and product development require early consideration to ensure the appropriate tools and data are in place once advanced leads and candidates are identified. We would consider funding for projects aimed at the following issues:

	<ul>
		<li>Identifying candidate biomarkers of efficacy for non-hormonal contraceptive mechanisms-of-action, including biochemical or imaging markers, that can be applied to preclinical in vivo models and, ideally, that could be applicable for validation in human clinical studies.</li>
		<li>Improving our understanding and prediction of reproductive tract and reproductive tissue pharmacokinetics to assist in building PK/PD models and enable early dose selection and safety risk evaluation.</li>
		<li>Improved and tractable in vivo models for contraceptive efficacy that overcome limitations of existing rodent and primate models.</li>
		<li>Innovative methods for early assessment of safety, toxicity, and side effect risk, with particular emphasis on the potential for endocrine disruption and bleeding side effects.</li>
	</ul>
	</li>
</ol>

There are clear thematic overlaps in the focus areas described above, and we would be happy to receive proposals that are directed at multiple focus areas, so long as the application demonstrates strength in all related areas of proposed work.

Award

This Grand Challenges request for proposals intends to fund individual awards of up to USD $2 million and for up to 3 years, based on the scope of the proposed project. The proposed budget must realistically reflect the technical work and project deliverables within a 3-year timeframe; in some cases, a smaller budget may be justified to establish initial proof-of-concept. Budgets and scope may be negotiated with applicants as part of the review process to ensure the foundation’s ability to fund a robust and balanced portfolio with existing available budget (see the Review Process as detailed in the Rules and Guidelines).

Successful award recipients may have the opportunity to apply for additional funding at the end of the grant period, based on technical success, portfolio fit, and continued strategic alignment with the foundation’s priorities. We reserve the right to determine eligibility for subsequent funding for this call based on these criteria.

"That's the idea behind Grand Challenges - to focus bright scientists on the problems of the poorest, take some risks, and deliver results." Bill Gates
"Family planning and access to contraception - including information, supplies, and services - is an issue that I am passionate about, and it has become one of my personal priorities at the foundation. 
I believe it's one of the most urgent issues of our time." Melinda Gates
<h2>Background</h2>
Family planning is one of the most cost-effective ways to reduce maternal, infant and child mortality and contributes to the empowerment of women and families, as well as the expansion of opportunities for economic development. In recent decades, there have been tremendous improvements in the reproductive health of women in low resource settings. Global efforts have substantially accelerated progress toward the goal of reaching 120 million additional users of contraception by 2020 in the world’s poorest countries, an achievement well worth celebrating. Nonetheless, it is estimated that over 214 million women in developing countries have an unmet need for modern contraception.
While current contraceptive methods for women include exceptionally safe and effective options, not all methods are suitable for or acceptable to all women at all stages of their reproductive lives, and concerns about undesirable side effects remain a significant barrier to greater uptake and continued use of existing methods. As a result, women who desire to avoid pregnancy often find themselves without viable options that meet their needs. In particular, changes in uterine bleeding patterns are associated with use of hormonal contraceptive methods and copper intrauterine devices and, combined with access challenges and social or religious norms related to contraceptive use or menstrual bleeding, contribute to high discontinuation rates for these methods (up to 40% in the first year of use). While the concept of developing a non-hormonal pharmaceutical contraceptive with an improved tolerability profile as a suitable alternative has been promoted through research efforts and publications, a focused discovery effort has not been systematically pursued.
<h2>THE CHALLENGE</h2>
The Bill &amp; Melinda Gates Foundation is committed to a long-term vision of expanding contraceptive options for the most vulnerable women in low-resource settings through development of new methods that better align with women’s preferences. Contraceptive product innovation will be required to achieve this goal. Specifically, the emphasis for this work is on developing safe and effective non-hormonal contraceptive agents with both improved overall tolerability and a side effect profile differentiated from hormonal methods. This emphasis is based on an understanding that overall tolerability of and side effects from hormonal methods present real and meaningful barriers to women realizing their reproductive intentions.
This vision demands establishment of a strong research foundation upon which to build a robust pipeline of product candidates, recognizing that the attrition rate of products in preclinical and clinical development will likely be substantial due to the high bar for safety and efficacy. In order to establish a set of critical reproductive biology and early stage discovery capabilities, in-source novel ideas from other areas of science, and improve the knowledge base needed to support such an effort, the foundation is launching the "Accelerating Discovery for Non-Hormonal Contraceptives" Grand Challenge in 2020. The goal of this Grand Challenge is to identify new approaches and concepts directed at the characterization of novel contraceptive drug targets, the identification of active contraceptive compounds useful for target validation and proof-of-principle studies, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&amp;D.
The ultimate outcome driving the foundation’s investment in this area is the discovery new drug candidates that i) provide safe and effective contraception, ii) do not rely on systemic administration of reproductive steroid hormones or act through perturbation of sex steroid pathways, and iii) are suitable and appropriate for deployment in a low resource setting. The focus of this Grand Challenge is on broadly enhancing the research ecosystem for contraceptive discovery and advancing novel and bold ideas that can accelerate drug discovery in this field. We do not expect that novel contraceptive product candidates ready for entry into preclinical development will be identified in this early stage of funding. We anticipate, however, that projects funded through this Grand Challenge will identify new drug discovery approaches and technologies that have yet to be effectively applied to contraceptive R&amp;D. We expect to engage a broad range of expertise across disciplines in a collaborative and coordinated research program. It is anticipated, but not guaranteed, that success in these efforts would justify additional investment in a broader drug discovery effort by the Bill &amp; Melinda Gates Foundation, with the goal of developing innovative non-hormonal contraceptive methods to better serve the needs of women.
Approach
As approaches to discovery of new drugs for other indications have become increasingly sophisticated, these advances have not been applied to field of contraceptives. As a result, critical technical barriers continue to hamper progress and limit our ability to effectively identify novel contraceptive agents. These barriers include, but are not limited to:
<ul><li>The inability to appropriately replicate in the laboratory a number of complex multi-cellular reproductive processes for the purposes of compound screening (e.g. ovulation);</li>
<li>Poor understanding of contraceptive drug targets associated with key fertility pathways, and a lack of validated and scalable approaches to validate and assay potential targets;</li>
<li>Lack of appropriate medium- to high-throughput phenotypic screening methodologies for identifying compounds capable of exerting a specific and potent contraceptive effect;</li>
<li>Lack of appropriate in vitro and in vivo preclinical assays and biomarkers to assess i) the efficacy of agents targeting novel contraceptive mechanisms and ii) the potential side effects of novel agents.</li>
</ul>It is our belief that these challenges can be addressed, and that doing so will create substantial new opportunities for contraceptive drug discovery. We seek to leverage advances in other areas of reproductive biology, both basic and applied, and emerging technologies in drug discovery to establish a suite of capabilities that can support a robust drug discovery program. It is not our intention to establish fully integrated end-to-end drug discovery capabilities with individual institutions through this program, but rather to fund a network of researchers, with each bringing a unique approach, and facilitate interactions between partners to maximize impact. Applicants should keep this in mind when articulating a project plan and focus on the key strengths that their expertise, approach, and technology can provide. Proposals should be aligned with one or more of the funding focus areas outlined below.
We are looking for proposals that:
<ul><li>Engage scientists across a variety of disciplines, including those new to the field of contraceptive R&amp;D;</li>
<li>Demonstrate innovative thinking by applying or incorporating concepts, methods or technologies not currently being used for contraceptive discovery;</li>
<li>Present concepts and strategies that are "off the beaten track", significantly radical in conception, and daring in premise;</li>
</ul>We will NOT consider funding for:
<ul><li>Proposals focused on development of male contraceptives, including work on sperm-based approaches that could only feasibly be applied as vaginal methods;</li>
<li>Proposals targeting the endometrium for the prevention on embryo implantation;</li>
<li>Proposals on novel drug delivery systems for contraception;</li>
<li>Discovery of adjunct or complementary molecules intended for co-delivery with hormonal contraceptive regimens;</li>
<li>Basic studies of human reproductive biology without a clear connection to enabling non-hormonal contraceptive discovery;</li>
<li>Pre-clinical or clinical development of advanced leads and candidates;</li>
<li>Social science, marketing, or acceptability studies related to contraceptive use and uptake.</li>
</ul>Awardees through this Grand Challenge may have the opportunity to access other Gates Foundation-funded resources, technology platforms, and grantee networks to help support their projects, facilitated by their Gates Foundation Program Officer. Applicants should, as completely as possible, describe what the proposed project will deliver within the scope of the application and the potential path forward, even if that encompasses activities that are beyond the scope of the current funding opportunity. Applicants invited to submit full proposals following LOI review (see the Review Process as detailed in the Rules and Guidelines) should expect to include critical milestones and relevant go/no-go decisions for the proposed project.
Funding Focus Areas:
<ol><li>Biological Assay Development
Many aspects of female reproduction remain challenging to replicate or model in a tractable, physiologically relevant, and highly reproducible fashion, but such tools and models will be fundamentally important to identifying and profiling contraceptive drug targets and contraceptive compounds. A better toolset of in vitro assays is needed that can recapitulate oocyte and follicle development, follicle selection, follicular rupture/ovulation, corpus luteum formation, cumulus-oocyte complex dynamics, and fertilization, including peri-fertilization events. New models should focus on assay tractability as well as establishing physiological relevance and modeling closely relevant features of the in vivo environment. Applicants seeking to develop such systems should clearly describe the planned approach and how this would improve upon existing methods. Including approaches to validate with human samples or human genetics/genomic information would be viewed favorably. Proposals should include a discussion on how assays will be standardized, validated, and scaled, including where possible the use of genetic or chemical probes as positive controls to demonstrate biologically relevant outcomes following assay perturbation.
</li>
<li>Drug Target Identification and Validation
In the past two decades, target-based drug discovery approaches have become increasingly sophisticated and powerful, but further and complementary approaches are needed to sustain a pipeline of potential drug targets and enhance our understanding of target biology. Emphasis will be placed on unbiased approaches to identify potential contraceptive drug targets. These may include (but are not limited to):
<ul><li>RNAi- or CRISPR-based methods utilizing a robust and relevant biological assay,</li>
<li>chemical genomics or proteomics linking probe compound activity to specific drug targets or pathways,</li>
<li>analyses of human infertility as a pathway to identify relevant drug targets, or</li>
<li>artificial intelligence-enabled approaches to target identification.</li>
</ul>
	Target characterization and validation efforts should focus on the determination of whether any particular gene that is critical for a reproductive process is vulnerable to inhibition by a small molecule inhibitor (using, for example, tunable knockdown or inducible degradation techniques), can likely be safely modulated by such an inhibitor (including assessment of roles in somatic tissue and activity of closely related homologs), and is likely to provide the desired contraceptive effect at realistic levels of inhibition (as opposed to complete loss-of-function). Applicants should clearly describe the critical assays, methods, or approaches they are proposing to underpin this work, and describe how such approaches will yield compelling and relevant data that could be used to support entry of identified targets into target-based drug discovery activities.
</li>
<li>Chemical genomics, probe generation, pilot screening
The availability of active compounds that interfere with key steps in fertility would open up many avenues for further biological exploration and target validation, but methods for screening small compound libraries for chemical probe discovery are currently limited. Applications will be considered that propose small pilot-scale screening in complex systems for the purposes of identifying active compounds interfering with key reproductive functions. Applicants must detail how screening systems will be developed, tested, and validated in a format suitable for testing compounds, and should detail the type and source of chemical libraries that would be utilized. Biologically-informed hypotheses may be proposed to select mechanism- or target class-focused libraries as a starting point. We will not consider applications for screening of a single proposed target, but mechanism-focused approaches that interrogate multiple targets involved in a key reproductive process would be considered. Applicants must then describe an approach to deduce the specific targets of compounds identified in cell-based screens and demonstrate concordance between target-based activity and functional activity in validated in vitro systems.
</li>
<li>Contraceptive Antibodies
While the cost and practicality of antibody-based therapeutics has historically been a challenge, particularly for application in a low resource setting, new advances in antibody half-life extension and cost-effective production open up the possibility that antibodies may be a more tractable option in the future, particularly if used in an "on demand" contraceptive modality. Moreover, this may allow consideration of targets that would otherwise not be amenable to small molecule inhibitors and may provide an enhanced safety window. Applications focused on contraceptive antibodies should clearly articulate the data supporting the validation of the proposed antigen target, the methods to be used for antibody identification, and the assays to be used relevant to determination of antibody function.
(Note: the foundation is not accepting applications based on contraceptive immunization as an intervention modality, though such approaches could be applied experimentally for target validation.)
</li>
<li>Translational Science/Preclinical Evaluation Tools
In addition to target and hit discovery activities, downstream aspects of drug and product development require early consideration to ensure the appropriate tools and data are in place once advanced leads and candidates are identified. We would consider funding for projects aimed at the following issues:
<ul><li>Identifying candidate biomarkers of efficacy for non-hormonal contraceptive mechanisms-of-action, including biochemical or imaging markers, that can be applied to preclinical in vivo models and, ideally, that could be applicable for validation in human clinical studies.</li>
<li>Improving our understanding and prediction of reproductive tract and reproductive tissue pharmacokinetics to assist in building PK/PD models and enable early dose selection and safety risk evaluation.</li>
<li>Improved and tractable in vivo models for contraceptive efficacy that overcome limitations of existing rodent and primate models.</li>
<li>Innovative methods for early assessment of safety, toxicity, and side effect risk, with particular emphasis on the potential for endocrine disruption and bleeding side effects.</li>
</ul></li>
</ol>There are clear thematic overlaps in the focus areas described above, and we would be happy to receive proposals that are directed at multiple focus areas, so long as the application demonstrates strength in all related areas of proposed work.
Award
This Grand Challenges request for proposals intends to fund individual awards of up to USD $2 million and for up to 3 years, based on the scope of the proposed project. The proposed budget must realistically reflect the technical work and project deliverables within a 3-year timeframe; in some cases, a smaller budget may be justified to establish initial proof-of-concept. Budgets and scope may be negotiated with applicants as part of the review process to ensure the foundation’s ability to fund a robust and balanced portfolio with existing available budget (see the Review Process as detailed in the Rules and Guidelines).
Successful award recipients may have the opportunity to apply for additional funding at the end of the grant period, based on technical success, portfolio fit, and continued strategic alignment with the foundation’s priorities. We reserve the right to determine eligibility for subsequent funding for this call based on these criteria.

Grand Challenges seeks new approaches and concepts for the characterization of contraceptive drug targets, the identification of active contraceptive compounds, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&amp;D. We seek to leverage advances in reproductive biology, both basic and applied, and emerging technologies in drug discovery to establish a suite of capabilities that can support drug discovery in this challenging area.

Accelerating Discovery for Non-Hormonal Contraceptives

Date open: 30 Oct 2019 | Deadline: 5 Dec 2019 - 11:30am PST

**NOTE: This opportunity is only open to participants who registered for and attended the Grand Challenges Annual Meeting in Addis Ababa, Ethiopia.

<h2>The Opportunity</h2>

We believe the Grand Challenges Annual Meetings present a great opportunity to engage some of the brightest scientific minds, learn about challenges in global health and development, and explore new approaches and catalyze collaboration to accelerate innovation for impact in solving the world’s most urgent global health and development problems. In Addis Ababa, the Grand Challenges meeting convened a diverse set of organizations and participants across the 11 content-area tracks listed below (see the <a href="https://custom.cvent.com/B6E596DEAC6A4A7FB1467497AE4FF54B/files/event/8106e715917547e08c110675bcc58d5f/55498a4380f34683aac5ff5952b975ec.pdf" target="_blank">2019 GC Annual Meeting Agenda </a>for full track information). In addition to the scientific track sessions, the meeting included inspiring plenary talks, poster sessions, and plenty of opportunities for connection, discussion, and learning. But an engaging meeting is not enough; we also seek tangible outcomes. The meeting should inspire members of the Grand Challenges community to drive forward high-risk, high-reward ideas to address the biggest health and development challenges.

To maintain the meeting’s spirit of accelerating innovation to impact after the meeting ends, we are providing a grant opportunity to build on your participation in the Grand Challenges meeting.

With the meeting location in Addis Ababa, and the Ethiopian Ministry of Health and African Union among the meeting co-hosts, we seek to continue the meeting’s focus on the capacity and strengths of the African innovation, research, and development ecosystem.

<h2>The Challenge – a Call to Action</h2>

While at the Addis Ababa Grand Challenges meeting, did you…

<ul>
	<li>meet a new collaborator and develop a plan of action?</li>
	<li>learn about a new problem you think you can solve?</li>
	<li>learn something new that you can apply to the problem you are currently working on?</li>
</ul>

If so, we want to see your best idea! We invite you to submit a two-page application that proposes new work on a topic relevant to any of the meeting tracks and describes how it is grounded in the inspiration, information, and perspective you gained through your participation in the meeting.

In determining the proposals to fund, we will prioritize proposals that include new collaborations, particularly those that involve expertise, infrastructure, and/or capacity based on the African continent.*

Each eligible meeting participant will have one (1) opportunity to apply as the Primary Applicant. Primary Applicants have two funding levels to choose from:

<ul>
	<li>$200,000 USD Collaborative Pilot award; or</li>
	<li>$100,000 USD Pilot award</li>
</ul>

Both funding levels will have an 18 month grant term. Collaborative awards require the participation of at least two GCAM participants from different institutions. While restricted to one application as the primary applicant, eligible meeting participants may participate as collaborators in multiple collaborative pilot applications. Priority will be given to new or newly expanded collaborations, rather than to existing partners seeking new funding. See the Call to Action Rules and Guidelines [here] for more information.

Please note that while Pilot and Collaborative Pilot proposals were received in roughly equivalent numbers last year, reviewers were more excited by new collaborations. The <a href="https://medium.com/@trevormundel/we-believe-in-the-power-of-collaboration-so-we-designed-a-grant-competition-to-incentivize-it-ce04494cc1d7" target="_blank">award announcement</a> and <a href="/grants/eyJzb3J0IjoiZGVzY2VuZGluZyIsInNvcnRGaWVsZCI6ImRhdGUiLCJudW1iZXJQZXJQYWdlIjoxMCwicGFnZU51bWJlciI6MH0=/eyJ5ZWFycyI6WyIyMDE5Il0sImNoYWxsZW5nZXMiOlsiMTI5Il0sInRlcm1zIjpbXSwiaW5pdGlhdGl2ZXMiOltdLCJsb2NhdGlvbnMiOltdfQ==">final portfolio</a> from the <a href="https://gcgh.grandchallenges.org/challenge/2018-grand-challenges-annual-meeting-call-action" target="_blank">Call to Action 2018</a> reflect that prioritization, and we expect similar results from this call.

Timeline

We seek to harness the energy and excitement of the meeting to test creative new ideas or new collaborations fostered by the meeting. To that end, proposals will be due on December 5, 2019 (one month from the meeting close), and we anticipate funding decisions to be made in the first quarter of 2020.

2019 GCAM tracks

<ul>
	<li>African Innovation Research and Development Ecosystem</li>
	<li>Crop Productions Analytics at Scale: Innovations in Ground Truthing</li>
	<li>DevelopmentXChange: Accelerating Adoption of Maternal and Newborn Global Health Innovations</li>
	<li>Gender Norms and Programmatic Impact</li>
	<li>Growth and Resilience: Optimizing Birth, Growth and Development</li>
	<li>Improving Development Outcomes with Digital Tools</li>
	<li>Leveraging Pathogen Genetic Sequencing in Africa</li>
	<li>Optimizing Drug Discovery and Translation</li>
	<li>Pest and Disease Surveillance and Epidemiology</li>
	<li>Scaling Innovation with a Gender Lens</li>
	<li>Vaccines and Global Health Technology</li>
</ul>

Applicants are strongly encouraged to review the track abstracts provided in the <a href="https://custom.cvent.com/B6E596DEAC6A4A7FB1467497AE4FF54B/files/event/8106e715917547e08c110675bcc58d5f/55498a4380f34683aac5ff5952b975ec.pdf" target="_blank">2019 GC Annual Meeting Agenda</a>. Abstracts can be found beginning on page 6. The most common reason for declined proposals last year was a lack of fit with the meeting content.

Apply

Please find application instructions <a href="/sites/default/files/files/gcam_2019_cta_application_instructions.pdf" target="_blank">here</a> and submit your proposal <a href="https://gatesfoundation.smapply.io/" target="_blank">here</a>. We look forward to reading your application.

2019 Grand Challenges Annual Meeting Call-to-Action

June 10, 2020 Update: We are proud to announce 28 grants of $100,000 each in the Voices for Economic Opportunity Grand Challenge, to a wide array of organizations that will work to correct mistaken assumptions and improve understanding of the barriers to economic mobility through the stories of those who experience poverty. Read the <a href="https://www.gatesfoundation.org/Media-Center/Press-Releases/2020/06/Changing-the-National-Conversation-About-Poverty-and-Economic-Mobility" target="_blank">press release</a> and <a href="https://www.gatesfoundation.org/TheOptimist/Articles/coronavirus-grand-challenge-ryan-rippel" target="_blank">blog post</a>.

Over the past few years, our team at the Bill &amp; Melinda Gates Foundation has been travelling to communities across the U.S. to meet with people where they live to learn about economic mobility and opportunity from their perspectives. We hoped that what they shared would help us work effectively alongside the many successful organizations that have spent years fighting for more opportunity for more Americans. We heard them clearly when they spoke about the deeply rooted, entangled challenges that make these issues so complex. There are no silver bullet solutions for communities suffering the effects of deindustrialization and no easy fix for structural racism.

One important theme of those conversations was the huge gap between longstanding assumptions about poverty and the reality of millions of Americans’ lives. These ingrained but inaccurate assumptions, we heard over and over again, lead to a misdiagnosis of the problem, which in turn generates ineffective and inadequate solutions.

This call for ideas is designed to support individuals and organizations interested in contributing to the long-term work of correcting mistaken assumptions and improving understanding of poverty through the actual stories of those that experience poverty – in a way that represents the core factors and challenges. This is a first step for us. We look forward to building ongoing collaborations with activists, organizers, and other committed partners to address the range of priorities they have laid out.

<h2>OVERVIEW</h2>

We're seeking creative, compelling ideas from individuals and organizations from all sectors in the U.S. to elevate diverse voices and broaden the national conversation about poverty and economic mobility. Anyone with a great concept is welcome to apply for a $100,000 grant to develop their idea.

<h2>BACKGROUND</h2>

In May 2018, the Bill &amp; Melinda Gates Foundation embarked on a new $158-million program in U.S. Economic Mobility and Opportunity which seeks to increase the number and diversity of actors working in coordination to address barriers to economic mobility. Myths and misconceptions about poverty are one of the most stubborn of these barriers. Since our announcement, we’ve seen a groundswell of interest in challenging existing ideas about who experiences poverty, bringing to light the contributions they offer to American society, and highlighting the structural and historic barriers they face including race, gender, and geography (among other factors).

In collaboration with the Robert Wood Johnson Foundation, the W.K. Kellogg Foundation and the Raikes Foundation, we seek to build on the understanding of poverty gleaned from the <a href="https://www.mobilitypartnership.org/" target="_blank">U.S. Partnership on Mobility from Poverty</a> initiative and to combat inaccurate assumptions about poverty, deservingness, income, and wealth gaps that are widespread and harmful. Each of these funders will bring to this collaboration their unique expertise and experience working to address inequity in the United States. Moving from prevailing stories rooted in misconceptions and stereotypes to ones rooted in shared values, history, systemic solutions, equity, and human dignity is a crucial step in dramatically increasing economic mobility.

We recognize there is a vigorous debate about how to equitably close economic gaps and create equitable opportunity and mobility for more Americans. Many voices across the country are already immersed in this conversation. Yet too many voices are still being left out.

<h2>THE CHALLENGE</h2>

The goal of this challenge is to elevate diverse voices that can help broaden the conversation about the issues inhibiting economic mobility and generate deeper awareness and actionable understanding. Most Americans believe it is right to help others, so that they may have the opportunity to live healthy and productive lives. Yet skepticism exists about the efficacy of anti-poverty programs in the U.S. and deep-seated stereotypes remain about people experiencing poverty and who deserves to rise out of it. Many community practitioners and social movement leaders in the U.S. are already working to address this challenge. Still, there is a need for new ways of bringing personal stories to life to help others better understand why people fall into or remain hindered by barriers that impede their ability to advance and what the obstacles to building and maintaining economic security are. We seek proposals for creative, scalable, strategic new ways to generate awareness of the structural and historic barriers to economic mobility; to communicate that poverty is not just something that happens to other people and everyone is deserving of the chance to move out of it; and to change the predominant misconceptions about poverty in a way that creates the conditions for effective programs and policies to be adopted by the public and private sectors.

What we are looking for:

We will give highest priority to proposals that:

<ul>
	<li>Highlight barriers to economic mobility as well as the impact of biases, intersectionality, and ideas around deservingness related to race, gender, ethnicity, religion, national origin, sexual orientation, age, physical and mental health, ability, and geography</li>
	<li>Highlight the voices of individuals experiencing poverty</li>
	<li>Highlight ideas for distributing these perspectives</li>
</ul>

We seek to fund a portfolio of projects that:

<ul>
	<li>Shift the conversation from one that stigmatizes to one that demonstrates “this could be someone I know and value,” signifying that we all have a common interest in expanding economic mobility and dignity</li>
	<li>Move from a depiction of individuals as victims to protagonists with agency who are deserving of opportunity</li>
	<li>Change from a sole focus on lack of money to money, power, agency, and dignity</li>
	<li>Pivot from characterizations of personal failures and deficits to the ongoing importance of individual and collective responsibility and a general consensus that the status quo undermines American democracy and society</li>
	<li>Creatively use citizen voice and data to support communications in a way that generates a deeper understanding of structural and historic barriers to mobility</li>
	<li>Provide insight into workable solutions for overcoming intersecting stereotypes and deep seeded values of deservingness that generate biases based on race, gender, ethnicity, religion, national origin, sexual orientation, age, physical and mental health, ability, and geography</li>
	<li>Engage partners with diverse expertise and types of resources</li>
</ul>

A few of the many types of concepts we will consider include (but are not limited to):

<ul>
	<li>Integrating lessons learned from past or present poverty-alleviation programs, both successes and failures</li>
	<li>Engaging a range of voices that highlights the causes and consequences of poverty and identifies key windows of opportunity for the most effective change</li>
	<li>Incorporating technology, digital platform, or social network ideas with demonstrated value in enhancing dissemination in support of positive social change</li>
</ul>

We will not consider funding for:

<ul>
	<li>Projects centered entirely around donations made by individuals</li>
	<li>Projects focused on emergency relief or crisis response</li>
	<li>Academic research without a clear objective to solve a public understanding problem</li>
	<li>Initiatives limited to specific organizations</li>
	<li>Projects earmarking foundation funds for lobbying activity (e.g., attempts to influence legislation or legislative action) or efforts to influence political campaigns for public office</li>
	<li>Projects focused outside of the United States</li>
</ul>

<h2>HOW WE WILL EVALUATE PROPOSALS</h2>

Proposals will be reviewed against the following criteria:

<ul>
	<li>Responsiveness to the challenge: Does the proposal address the challenges described above? Please note the types of projects above that will not be funded.</li>
	<li>Innovative approach: Does the idea address the defined problem in an uncommon way or provide a creative approach to the problem outlined? Does the proposal describe how the project varies from current approaches, or offers new premises or hypotheses to test?</li>
	<li>Likelihood of success: Does the proposal include a clear and realistic rationale for success?</li>
	<li>Defined target audience(s): Does the approach leverage insights about a specific target audience(s) and design content that is most likely to move them?</li>
	<li>Efficient use of channels: Does the concept include technology and/or digital platforms currently being used at scale? Does the proposal seek to utilize existing infrastructure in communities?</li>
	<li>Collaborative design: Does the concept include plans for engaging a set of partners? Does the idea involve individuals or organizations with different skill sets coming together?</li>
	<li>Emphasis on lived experience: Does the concept help the broader U.S. public connect with people experiencing poverty and advance the agency of those experiencing poverty?</li>
</ul>

<h2>ABOUT OUR COLLABORATION</h2>

The Bill &amp; Melinda Gates Foundation has collaborated with the Robert Wood Johnson Foundation, the W.K. Kellogg Foundation and the Raikes Foundation to issue this call for proposals in its Grand Challenges Program. Subject to internal approval processes, the foundations anticipate funding successful proposals, and we hope other philanthropies will join us along the way.

Over the past few years, our team at the Bill &amp; Melinda Gates Foundation has been travelling to communities across the U.S. to meet with people where they live to learn about economic mobility and opportunity from their perspectives. We hoped that what they shared would help us work effectively alongside the many successful organizations that have spent years fighting for more opportunity for more Americans. We heard them clearly when they spoke about the deeply rooted, entangled challenges that make these issues so complex. There are no silver bullet solutions for communities suffering the effects of deindustrialization and no easy fix for structural racism.
One important theme of those conversations was the huge gap between longstanding assumptions about poverty and the reality of millions of Americans’ lives. These ingrained but inaccurate assumptions, we heard over and over again, lead to a misdiagnosis of the problem, which in turn generates ineffective and inadequate solutions.
This call for ideas is designed to support individuals and organizations interested in contributing to the long-term work of correcting mistaken assumptions and improving understanding of poverty through the actual stories of those that experience poverty – in a way that represents the core factors and challenges. This is a first step for us. We look forward to building ongoing collaborations with activists, organizers, and other committed partners to address the range of priorities they have laid out.
<h2>OVERVIEW</h2>
We're seeking creative, compelling ideas from individuals and organizations from all sectors in the U.S. to elevate diverse voices and broaden the national conversation about poverty and economic mobility. Anyone with a great concept is welcome to apply for a $100,000 grant to develop their idea.
<h2>BACKGROUND</h2>
In May 2018, the Bill &amp; Melinda Gates Foundation embarked on a new $158-million program in U.S. Economic Mobility and Opportunity which seeks to increase the number and diversity of actors working in coordination to address barriers to economic mobility. Myths and misconceptions about poverty are one of the most stubborn of these barriers. Since our announcement, we’ve seen a groundswell of interest in challenging existing ideas about who experiences poverty, bringing to light the contributions they offer to American society, and highlighting the structural and historic barriers they face including race, gender, and geography (among other factors).
In collaboration with the Robert Wood Johnson Foundation, the W.K. Kellogg Foundation and the Raikes Foundation, we seek to build on the understanding of poverty gleaned from the <a href="https://www.mobilitypartnership.org/" target="_blank">U.S. Partnership on Mobility from Poverty</a> initiative and to combat inaccurate assumptions about poverty, deservingness, income, and wealth gaps that are widespread and harmful. Each of these funders will bring to this collaboration their unique expertise and experience working to address inequity in the United States. Moving from prevailing stories rooted in misconceptions and stereotypes to ones rooted in shared values, history, systemic solutions, equity, and human dignity is a crucial step in dramatically increasing economic mobility.
We recognize there is a vigorous debate about how to equitably close economic gaps and create equitable opportunity and mobility for more Americans. Many voices across the country are already immersed in this conversation. Yet too many voices are still being left out.
<h2>THE CHALLENGE</h2>
The goal of this challenge is to elevate diverse voices that can help broaden the conversation about the issues inhibiting economic mobility and generate deeper awareness and actionable understanding. Most Americans believe it is right to help others, so that they may have the opportunity to live healthy and productive lives. Yet skepticism exists about the efficacy of anti-poverty programs in the U.S. and deep-seated stereotypes remain about people experiencing poverty and who deserves to rise out of it. Many community practitioners and social movement leaders in the U.S. are already working to address this challenge. Still, there is a need for new ways of bringing personal stories to life to help others better understand why people fall into or remain hindered by barriers that impede their ability to advance and what the obstacles to building and maintaining economic security are. We seek proposals for creative, scalable, strategic new ways to generate awareness of the structural and historic barriers to economic mobility; to communicate that poverty is not just something that happens to other people and everyone is deserving of the chance to move out of it; and to change the predominant misconceptions about poverty in a way that creates the conditions for effective programs and policies to be adopted by the public and private sectors.
What we are looking for:
We will give highest priority to proposals that:
<ul><li>Highlight barriers to economic mobility as well as the impact of biases, intersectionality, and ideas around deservingness related to race, gender, ethnicity, religion, national origin, sexual orientation, age, physical and mental health, ability, and geography</li>
<li>Highlight the voices of individuals experiencing poverty</li>
<li>Highlight ideas for distributing these perspectives</li>
</ul>We seek to fund a portfolio of projects that:
<ul><li>Shift the conversation from one that stigmatizes to one that demonstrates “this could be someone I know and value,” signifying that we all have a common interest in expanding economic mobility and dignity</li>
<li>Move from a depiction of individuals as victims to protagonists with agency who are deserving of opportunity</li>
<li>Change from a sole focus on lack of money to money, power, agency, and dignity</li>
<li>Pivot from characterizations of personal failures and deficits to the ongoing importance of individual and collective responsibility and a general consensus that the status quo undermines American democracy and society</li>
<li>Creatively use citizen voice and data to support communications in a way that generates a deeper understanding of structural and historic barriers to mobility</li>
<li>Provide insight into workable solutions for overcoming intersecting stereotypes and deep seeded values of deservingness that generate biases based on race, gender, ethnicity, religion, national origin, sexual orientation, age, physical and mental health, ability, and geography</li>
<li>Engage partners with diverse expertise and types of resources</li>
</ul>A few of the many types of concepts we will consider include (but are not limited to):
<ul><li>Integrating lessons learned from past or present poverty-alleviation programs, both successes and failures</li>
<li>Engaging a range of voices that highlights the causes and consequences of poverty and identifies key windows of opportunity for the most effective change</li>
<li>Incorporating technology, digital platform, or social network ideas with demonstrated value in enhancing dissemination in support of positive social change</li>
</ul>We will not consider funding for:
<ul><li>Projects centered entirely around donations made by individuals</li>
<li>Projects focused on emergency relief or crisis response</li>
<li>Academic research without a clear objective to solve a public understanding problem</li>
<li>Initiatives limited to specific organizations</li>
<li>Projects earmarking foundation funds for lobbying activity (e.g., attempts to influence legislation or legislative action) or efforts to influence political campaigns for public office</li>
<li>Projects focused outside of the United States</li>
</ul><h2>HOW WE WILL EVALUATE PROPOSALS</h2>
Proposals will be reviewed against the following criteria:
<ul><li>Responsiveness to the challenge: Does the proposal address the challenges described above? Please note the types of projects above that will not be funded.</li>
<li>Innovative approach: Does the idea address the defined problem in an uncommon way or provide a creative approach to the problem outlined? Does the proposal describe how the project varies from current approaches, or offers new premises or hypotheses to test?</li>
<li>Likelihood of success: Does the proposal include a clear and realistic rationale for success?</li>
<li>Defined target audience(s): Does the approach leverage insights about a specific target audience(s) and design content that is most likely to move them?</li>
<li>Efficient use of channels: Does the concept include technology and/or digital platforms currently being used at scale? Does the proposal seek to utilize existing infrastructure in communities?</li>
<li>Collaborative design: Does the concept include plans for engaging a set of partners? Does the idea involve individuals or organizations with different skill sets coming together?</li>
<li>Emphasis on lived experience: Does the concept help the broader U.S. public connect with people experiencing poverty and advance the agency of those experiencing poverty?</li>
</ul><h2>ABOUT OUR COLLABORATION</h2>
The Bill &amp; Melinda Gates Foundation has collaborated with the Robert Wood Johnson Foundation, the W.K. Kellogg Foundation and the Raikes Foundation to issue this call for proposals in its Grand Challenges Program. Subject to internal approval processes, the foundations anticipate funding successful proposals, and we hope other philanthropies will join us along the way.

Voices for Economic Opportunity seeks to elevate new and diverse voices that can help broaden the conversation about the issues underlying economic mobility in the United States and generate deeper awareness and actionable understanding. Application is open to U.S.-based investigators.

Voices for Economic Opportunity

Note: we initially targeted an application window of 4 weeks; however, we have now expanded that to 8 weeks and will be accepting proposals until March 25, 2019.

The Neglected Tropical Diseases (NTD) team at the Bill &amp; Melinda Gates Foundation supports global efforts to control, eliminate, and eradicate NTDs. The team focuses on seven of the ten <a href="http://unitingtocombatntds.org/wp-content/uploads/2017/11/london_declaration_on_ntds.pdf" target="_blank">London Declaration</a> diseases, as well as on cross-cutting efforts to improve the quality and impact of NTD programs through a variety of levers, including data systems. Strengthening NTD data systems and ensuring use of quality data for programmatic decision-making at the country, regional, and global levels are priority components of these cross-cutting efforts.

National NTD programs rely on timely and quality data to make decisions throughout the duration of the program. The quality of these data ultimately depends on the systems, tools, and processes at the points-of-collection, collation, and analysis at sub-national and national levels. Many of the current data-related tools and approaches used by NTD programs are sub-optimal and hinder the ability of the national program to deliver. Specifically, a limited NTD data system can lead to an inaccurate understanding of program performance and reduced likelihood of achieving control and elimination goals. Moreover, poor quality country data and data systems introduces delay and inaccuracies in regional and global reporting, drug forecasting, and inefficient allocation of resources.

This Grand Challenge seeks innovative ideas for how to improve the quality, completeness, and timeliness of routine NTD data and ensure programmatic decision-making is based on the best available data. Such outcomes will help target interventions to all at-risk populations and achieve high intervention coverage and maximal impact on infection and morbidity.

Neglected Tropical Diseases Data Innovation Incubator

**NOTE: This opportunity was open only to invited participants at the 2018 Grand Challenges Annual Meeting held in Berlin, Germany.

<h2>The Opportunity</h2>

We believe the Grand Challenges Annual Meetings (GCAM) present a great opportunity to engage some of the brightest scientific minds, learn about challenges in global health and development, and explore new approaches and collaborations to tackle the toughest problems. In Berlin, the Grand Challenges meeting convened a diverse set of organizations and participants across the 12 content-area tracks listed below. In addition to the scientific track sessions, the meeting included inspiring plenary talks, poster sessions, and plenty of opportunities for connection, discussion, and learning. But we also seek tangible outcomes and hope the meeting inspires members of the Grand Challenges community to drive forward high-risk, high-reward ideas to address the biggest health and development challenges.

To keep the meeting’s spirit of accelerating innovation to impact going after the meeting ends, we are providing a grant opportunity to build on your participation in the Grand Challenges meeting.

<h2>The Challenge – a Call to Action</h2>

While at the Berlin Grand Challenges meeting, did you…

<ul>
	<li>learn about a new problem you think you can solve?</li>
	<li>learn something new that you can apply to the problem you are currently working on?</li>
	<li>meet a new collaborator and develop a plan of action?</li>
</ul>

If so, we want to see your best idea! We invite you to submit a two-page application that proposes new work on a topic relevant to any of the meeting tracks and describes how it is grounded in the inspiration, information, and perspective you gained through your participation in the meeting. We also strongly encourage you to review the foundation’s <a href="https://www.gatesfoundation.org/What-We-Do" target="_blank">strategies and priorities</a> since funding is available only for projects that fit within these strategies.

Each eligible meeting participant will have one (1) opportunity to apply as the primary investigator (PI) for one of two funding levels:

<ul>
	<li>$100,000 USD pilot award</li>
	<li>$200,000 USD collaborative pilot award</li>
</ul>

Both funding levels will have an 18 month grant term. Collaborative awards must be between at least two GCAM participants from different institutions. While restricted to one application as the PI, eligible meeting participants may participate in multiple collaborative pilot applications. Priority will be given to new or newly expanded collaborations, rather than to existing partners seeking new funding. See the GCAM Rules and Guidelines for more information.

Timeline

We seek to harness the energy and excitement of the meeting to test creative new ideas or new collaborations fostered by the meeting. To that end, proposals will be due on November 19, 2018 (one month from the meeting close), and we anticipate funding decisions to be made in early 2019.

2018 GCAM tracks

<ul>
	<li>Crop Research</li>
	<li>Developments in Research &amp; Development Against Antimicrobial Resistance</li>
	<li>From Innovation to Impact</li>
	<li>Growth and Resilience</li>
	<li>Health Systems Strengthening and Health Crisis Prevention</li>
	<li>National Surveillance Systems to Support Decision Agriculture Under Climate Change</li>
	<li>Optimizing Drug Discovery and Translation</li>
	<li>Pest and Disease Surveillance for Human, Livestock, and Crop Health</li>
	<li>Strengthening African Research and Development Ecosystems</li>
	<li>Unlocking the Power of Adolescents Through Innovation</li>
	<li>Vaccines and Global Health Technology</li>
	<li>What’s Next for Next Generation Sequencing (NGS) – A Role in Precision Public Health</li>
</ul>

2018 Grand Challenges Annual Meeting Call-to-Action

<h2>The Grand Challenge</h2>

(Facilitating innovation requires understanding) how do we create ecosystems that promote creativity…that promote innovation of benefit to the world and to humanity.<a href="#_ftn1" id="_ftnref1">[1]</a>&nbsp; 
Eliane Ubalijoro, McGill University, GCE Grantee

The net effect of Grand Challenges will be a massive return – these investments, really, will be traceable to saving millions of lives.<a href="#_ftn2" id="_ftnref2">[2]</a>&nbsp; 
Bill Gates

This is an all-hands-on-deck time. If we get there, we can make influenza history.<a href="#_ftn3" id="_ftnref3">[3]</a> 
Bruce Gellin, Sabin Vaccine Institute

<h2>Background</h2>

2018 marks the 100-year anniversary of the most severe influenza pandemic in recorded history, which killed an estimated 50 million people worldwide – more than the total deaths caused by the First World War. The subsequent influenza pandemics of 1957, 1968, 1977, and 2009, though milder than the 1918 pandemic, demonstrated the potential of influenza viruses to cause excessive morbidity, mortality, and, more generally, severe disruptions of healthcare systems. Clearly, the threat of pandemic influenza is very real. Also, influenza viruses pose a significant threat to humankind, with seasonal influenza disease leading to an estimated 290,000 – 650,000 deaths each year.

While vaccination remains the best tool for prevention of disease, the current influenza vaccines significantly underperform compared to the effective and durable vaccines used against other vaccine-preventable diseases around the world. One key reason for this comparatively reduced effectiveness is the influenza virus’ propensity for generating mutations in its surface antigens – the very targets of today’s vaccines. Furthermore, the predominant technologies for influenza vaccine production necessitate a protracted and inefficient manufacturing cycle and a huge supporting mechanism for biennial flu vaccine strain recommendations; by the time vaccines are ready for distribution – 6+ months after strain determination – the viruses circulating during next season may not match up well with those strains in vaccines leading to less than optimal vaccine effectiveness. Although other factors also contribute to poor vaccine effectiveness, the annual formulation changes, the cost of and limited access to current influenza vaccines (regardless of how well matched they are to circulating strains), and need for annual vaccinations are barriers to protecting against global seasonal influenza, particularly among those in low- and middle-income countries. Furthermore, at best they may only offer partial or minimal protection against emerging pandemic strains. Clearly, there is an unmet public health need for a transformative, game-changing universal influenza vaccine that will protect against all influenza strains for longer duration, alleviating the need for annual formulations and vaccinations and leading to a panacea for tackling pandemic and seasonal influenza disease threats.

Please see the Impatient Optimists blog: <a href="https://gcgh.grandchallenges.org/article/ending-pandemic-threat-grand-challenge-universal-influenza-vaccine-development" target="_blank">Ending the Pandemic Threat: A Grand Challenge for Universal Influenza Vaccine Development</a>.

<h2>Objectives</h2>

To find a game changing, universal solution to all these challenges, the Bill &amp; Melinda Gates Foundation and the Page Family are launching the "Universal Influenza Vaccine Development Grand Challenge" during the centenary year of the 1918 flu pandemic. The goal of this Grand Challenge is to identify novel, transformative concepts that will lead to development of universal influenza vaccines offering protection from morbidity and mortality caused by all subtypes of circulating and emerging (drifted and shifted) Influenza A subtype viruses and Influenza B lineage viruses for at least three to five years. It is envisaged that such a universal influenza vaccine would address the threat from both seasonal and pandemic influenza, thus alleviating the need for annual seasonal influenza vaccination campaigns, averting significant global morbidity and mortality, and better preparing the world for the next influenza pandemic.

While other funders are supporting development of universal Influenza vaccines, three things set this Grand Challenge apart. We seek to fund ideas that are bold and innovative, bridging the funding 'valley of death' to translate these novel approaches into products ready for human clinical trials. We also aim to encourage interdisciplinary collaboration and cross-fertilization of ideas from outside the traditional influenza research community. Third, we seek completely transformative approaches rather than incremental research.

Our collective belief is that innovation is catalyzed through rigorous collaboration and enriching of ecosystems, and we hope this Grand Challenge will stimulate creative thinking beyond the traditional influenza community. Although not exhaustive, examples of researchers and disciplines we would like to see further integrated and supported include computational and systems biologists, virologists, immunologists, bioinformatics, artificial intelligence, deep learning, machine learning, the HIV/AIDS and cancer immunotherapy research communities, etc. Fundamentally, we are looking for unconventional approaches that effectively drive or harness immune responses in desired ways and develop universal influenza vaccines that are ready to start clinical trials by 2021.

<h2>Approach</h2>

All proposals must be aligned with the Gates Foundation’s intervention Target Product Profile (iTPP). The iTPP (detailed in the Supporting Materials) describes the desired characteristics of a universal influenza vaccine. Most importantly, new vaccines should have the potential to be used in all age groups around the world, especially in developing countries. We are looking for affordable, effective vaccines that are suitable for delivery through existing immunization programs in-country, which has implications for product presentation and stability as well as for dosing route and schedule. The vaccines need to be broadly protective across Influenza A and B strains for a minimum of three to five years. Technologies will need to be scalable to meet worldwide demand.

We are looking for proposals that:

<ul>
	<li>Engage scientists across a variety of disciplines, including those new to the influenza field</li>
	<li>Demonstrate innovative thinking by incorporating concepts or technologies not currently being used within/addressed by the influenza vaccine field</li>
	<li>Present concepts and strategies that are “off the beaten track,” significantly radical in conception, and daring in premise.</li>
</ul>

Please note: grantees will have access to a wide-range of Gates Foundation-funded resources and technology platforms to support their projects

Examples of what we’re looking for may fall into broad categories:

<ol>
	<li>Antigen-centric: discovering new antigens/targets through Artificial Intelligence, Machine Learning, and/or Deep Learning approaches to get beyond traditional surface hemagglutinin</li>
	<li>Host-centric: approaches that (a) generate, enhance, or modify human immune protection, including sterilizing immunity (b) ensure longer term (possibly life-long) immune response (c) describe surrogates for longevity of immune response and (d) that target specific tissue or cell types for appropriate induction of local and systemic immunity leading to broader and longer protection</li>
	<li>Technology-centric: including (a) novel vaccine concepts, targets and constructs inspired by new observations or understanding about the nature of the influenza virus or the human response to it and (b) applications of radically new technologies for disease protection, such as production of immunogens using synthetic biology or radical genetic engineering approaches</li>
	<li>Enabling advances: including challenge models to quickly demonstrate safety and proof-of-concept for influenza vaccines</li>
</ol>

We also would be very happy to receive proposals that describe approaches for employing multiple interventions in combination.

In addition, we may entertain concept proposals related to use of DNA/RNA based delivery of longer acting universal influenza monoclonal antibody for passive prophylaxis or use of such monoclonals for exploring appropriate epitopes for universal influenza vaccine, if generally aligned with our iTPP.

We will NOT consider funding for:

<ul>
	<li>Marginal improvements in current seasonal influenza vaccines</li>
	<li>Precedented approaches using biosimilars to antigens or adjuvants currently in clinical development</li>
	<li>Basic studies of pathogen or human biology without a clear component that tests the potential for translation into product</li>
	<li>Development of assays, new reagents, adjuvants, or production technologies improving licensed and late-stage vaccines already in development</li>
	<li>Therapeutic monoclonal antibodies for treatment of influenza patients.</li>
</ul>

<h2>Award</h2>

Pilot awards ($250,000 up to $ 2 million)

This request for proposals intends to fund pilot awards of up to USD $2 million over 2 years, with the anticipation that one or more pilot projects, on demonstration of promising proof-of-concept data (e.g., from animal models), may be invited to apply for a full award up to USD $10 million. Full awards would be intended to fund IND-enabling and clinical studies.

Pilot awards do not include a requirement for an industry or translation partner but such partnerships would still be welcome. Industry is also welcome to apply directly for the pilot award. Successful pilot award recipients will have the opportunity to apply for additional funding, which could include grants, program related investments and/or contracts and must include a biopharmaceutical industry or other translational partner.

We reserve the right to determine eligibility for subsequent funding for this call based on these characteristics.

<h2>Suggested Reading</h2>

Please note: these suggested readings obviously do not represent an exhaustive list of all universal influenza vaccine activities and concepts and very few, if any, are likely to meet all the requirements of our iTPP (detailed in the Supporting Materials). We include these for illustrative purposes only and encourage applicants to understand and think beyond the ideas discussed below.

1. <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2018.00600/full" target="_blank">Arun Kumar, et al. (2018) Novel Platforms for the Development of a Universal Influenza Vaccine. Frontiers in Immunology. (doi:10.3389/fimmu.2018.00600)</a>.

2. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a029496.full.pdf+html" target="_blank">James E. Crowe, Jr. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Potential for a Universal Influenza Vaccine. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a029496).</a>

3. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a029413.full.pdf+html" target="_blank">Sarah F. Andrews, et al. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Immunogenetic Considerations Underlying B-Cell Biology in the Development of a Pan-Subtype Influenza A Vaccine Targeting the Hemagglutinin Stem. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a029413).</a>

4. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a028845.full.pdf+html" target="_blank">Florian Krammer, et al. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Toward a Universal Influenza Virus Vaccine: Potential Target Antigens and Critical Aspects for Vaccine Development. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a028845).</a>

5. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a028852.long" target="_blank">Davide Angeletti and Johnathan W. Yewdell. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Outflanking Antibody Immunodominance on the Road to Universal Influenza Vaccination. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a028852).</a>

6. <a href="https://www.sciencedirect.com/science/article/pii/S0264410X16300822?via%3Dihub" target="_blank">Francesco Berlanda Scorza, et al. (2016) Universal Influenza Vaccines: Shifting to Better Vaccines. Vaccine. (doi:10.1016/j.vaccine.2016.03.085).</a>

7. <a href="https://www.sciencedirect.com/science/article/pii/S0264410X16307447?via%3Dihub" target="_blank">Erin Sparrow, et al. (2016) Passive Immunization for Influenza through Antibody Therapies, a review of the pipeline, challenges and potential applications. Vaccine. (doi:10.1016/j.vaccine.2016.08.057).</a>

___________________________ 
<a href="#_ftnref1" id="_ftn1">[1]</a><a href="https://grandchallenges.org/video/grand-challenges-first-ten-years" target="_blank">Grand Challenges in Global Health – the First Ten Years</a> 
<a href="#_ftnref2" id="_ftn2">[2]</a><a href="https://grandchallenges.org/video/grand-challenges-first-ten-years" target="_blank">Grand Challenges in Global Health – the First Ten Years</a> 
<a href="#_ftnref3" id="_ftn3">[3]</a><a href="http://fortune.com/2018/03/21/universal-flu-vaccine/" target="_blank">Andrew Nusca, “Why We Need a Universal Flu Vaccine”, Fortune, 2018</a>

<h2>The Grand Challenge</h2>
(Facilitating innovation requires understanding) how do we create ecosystems that promote creativity…that promote innovation of benefit to the world and to humanity.1 
Eliane Ubalijoro, McGill University, GCE Grantee
 
 
 
The net effect of Grand Challenges will be a massive return – these investments, really, will be traceable to saving millions of lives.2 
Bill Gates
This is an all-hands-on-deck time. If we get there, we can make influenza history.3 
Bruce Gellin, Sabin Vaccine Institute
<h2>Background</h2>
2018 marks the 100-year anniversary of the most severe influenza pandemic in recorded history, which killed an estimated 50 million people worldwide – more than the total deaths caused by the First World War. The subsequent influenza pandemics of 1957, 1968, 1977, and 2009, though milder than the 1918 pandemic, demonstrated the potential of influenza viruses to cause excessive morbidity, mortality, and, more generally, severe disruptions of healthcare systems. Clearly, the threat of pandemic influenza is very real. Also, influenza viruses pose a significant threat to humankind, with seasonal influenza disease leading to an estimated 290,000 – 650,000 deaths each year.
While vaccination remains the best tool for prevention of disease, the current influenza vaccines significantly underperform compared to the effective and durable vaccines used against other vaccine-preventable diseases around the world. One key reason for this comparatively reduced effectiveness is the influenza virus’ propensity for generating mutations in its surface antigens – the very targets of today’s vaccines. Furthermore, the predominant technologies for influenza vaccine production necessitate a protracted and inefficient manufacturing cycle and a huge supporting mechanism for biennial flu vaccine strain recommendations; by the time vaccines are ready for distribution – 6+ months after strain determination – the viruses circulating during next season may not match up well with those strains in vaccines leading to less than optimal vaccine effectiveness. Although other factors also contribute to poor vaccine effectiveness, the annual formulation changes, the cost of and limited access to current influenza vaccines (regardless of how well matched they are to circulating strains), and need for annual vaccinations are barriers to protecting against global seasonal influenza, particularly among those in low- and middle-income countries. Furthermore, at best they may only offer partial or minimal protection against emerging pandemic strains. Clearly, there is an unmet public health need for a transformative, game-changing universal influenza vaccine that will protect against all influenza strains for longer duration, alleviating the need for annual formulations and vaccinations and leading to a panacea for tackling pandemic and seasonal influenza disease threats.
Please see the Impatient Optimists blog: <a href="https://www.impatientoptimists.org/Posts/2018/05/Ending-the-Pandemic-Threat-A-Grand-Challenge-for-Universal-Influenza-Vaccine-Development#.Ww8B2YeWyUn" target="_blank">Ending the Pandemic Threat: A Grand Challenge for Universal Influenza Vaccine Development</a>.
<h2>Objectives</h2>
To find a game changing, universal solution to all these challenges, the Bill &amp; Melinda Gates Foundation and the Page Family are launching the "Universal Influenza Vaccine Development Grand Challenge" during the centenary year of the 1918 flu pandemic. The goal of this Grand Challenge is to identify novel, transformative concepts that will lead to development of universal influenza vaccines offering protection from morbidity and mortality caused by all subtypes of circulating and emerging (drifted and shifted) Influenza A subtype viruses and Influenza B lineage viruses for at least three to five years. It is envisaged that such a universal influenza vaccine would address the threat from both seasonal and pandemic influenza, thus alleviating the need for annual seasonal influenza vaccination campaigns, averting significant global morbidity and mortality, and better preparing the world for the next influenza pandemic.
While other funders are supporting development of universal Influenza vaccines, three things set this Grand Challenge apart. We seek to fund ideas that are bold and innovative, bridging the funding 'valley of death' to translate these novel approaches into products ready for human clinical trials. We also aim to encourage interdisciplinary collaboration and cross-fertilization of ideas from outside the traditional influenza research community. Third, we seek completely transformative approaches rather than incremental research.
Our collective belief is that innovation is catalyzed through rigorous collaboration and enriching of ecosystems, and we hope this Grand Challenge will stimulate creative thinking beyond the traditional influenza community. Although not exhaustive, examples of researchers and disciplines we would like to see further integrated and supported include computational and systems biologists, virologists, immunologists, bioinformatics, artificial intelligence, deep learning, machine learning, the HIV/AIDS and cancer immunotherapy research communities, etc. Fundamentally, we are looking for unconventional approaches that effectively drive or harness immune responses in desired ways and develop universal influenza vaccines that are ready to start clinical trials by 2021.
<h2>Approach</h2>
All proposals must be aligned with the Gates Foundation’s intervention Target Product Profile (iTPP). The iTPP (detailed in the Supporting Materials) describes the desired characteristics of a universal influenza vaccine. Most importantly, new vaccines should have the potential to be used in all age groups around the world, especially in developing countries. We are looking for affordable, effective vaccines that are suitable for delivery through existing immunization programs in-country, which has implications for product presentation and stability as well as for dosing route and schedule. The vaccines need to be broadly protective across Influenza A and B strains for a minimum of three to five years. Technologies will need to be scalable to meet worldwide demand.
We are looking for proposals that:
<ul><li>Engage scientists across a variety of disciplines, including those new to the influenza field</li>
<li>Demonstrate innovative thinking by incorporating concepts or technologies not currently being used within/addressed by the influenza vaccine field</li>
<li>Present concepts and strategies that are “off the beaten track,” significantly radical in conception, and daring in premise.</li>
</ul>Please note: grantees will have access to a wide-range of Gates Foundation-funded resources and technology platforms to support their projects
Examples of what we’re looking for may fall into broad categories:
<ol><li>Antigen-centric: discovering new antigens/targets through Artificial Intelligence, Machine Learning, and/or Deep Learning approaches to get beyond traditional surface hemagglutinin</li>
<li>Host-centric: approaches that (a) generate, enhance, or modify human immune protection, including sterilizing immunity (b) ensure longer term (possibly life-long) immune response (c) describe surrogates for longevity of immune response and (d) that target specific tissue or cell types for appropriate induction of local and systemic immunity leading to broader and longer protection</li>
<li>Technology-centric: including (a) novel vaccine concepts, targets and constructs inspired by new observations or understanding about the nature of the influenza virus or the human response to it and (b) applications of radically new technologies for disease protection, such as production of immunogens using synthetic biology or radical genetic engineering approaches</li>
<li>Enabling advances: including challenge models to quickly demonstrate safety and proof-of-concept for influenza vaccines</li>
</ol>We also would be very happy to receive proposals that describe approaches for employing multiple interventions in combination.
In addition, we may entertain concept proposals related to use of DNA/RNA based delivery of longer acting universal influenza monoclonal antibody for passive prophylaxis or use of such monoclonals for exploring appropriate epitopes for universal influenza vaccine, if generally aligned with our iTPP.
We will NOT consider funding for:
<ul><li>Marginal improvements in current seasonal influenza vaccines</li>
<li>Precedented approaches using biosimilars to antigens or adjuvants currently in clinical development</li>
<li>Basic studies of pathogen or human biology without a clear component that tests the potential for translation into product</li>
<li>Development of assays, new reagents, adjuvants, or production technologies improving licensed and late-stage vaccines already in development</li>
<li>Therapeutic monoclonal antibodies for treatment of influenza patients.</li>
</ul><h2>Award</h2>
Pilot awards ($250,000 up to $ 2 million)
This request for proposals intends to fund pilot awards of up to USD $2 million over 2 years, with the anticipation that one or more pilot projects, on demonstration of promising proof-of-concept data (e.g., from animal models), may be invited to apply for a full award up to USD $10 million. Full awards would be intended to fund IND-enabling and clinical studies.
Pilot awards do not include a requirement for an industry or translation partner but such partnerships would still be welcome. Industry is also welcome to apply directly for the pilot award. Successful pilot award recipients will have the opportunity to apply for additional funding, which could include grants, program related investments and/or contracts and must include a biopharmaceutical industry or other translational partner.
We reserve the right to determine eligibility for subsequent funding for this call based on these characteristics.
<h2>Suggested Reading</h2>
Please note: these suggested readings obviously do not represent an exhaustive list of all universal influenza vaccine activities and concepts and very few, if any, are likely to meet all the requirements of our iTPP (detailed in the Supporting Materials). We include these for illustrative purposes only and encourage applicants to understand and think beyond the ideas discussed below.
1. <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2018.00600/full" target="_blank">Arun Kumar, et al. (2018) Novel Platforms for the Development of a Universal Influenza Vaccine. Frontiers in Immunology. (doi:10.3389/fimmu.2018.00600)</a>.
2. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a029496.full.pdf+html" target="_blank">James E. Crowe, Jr. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Potential for a Universal Influenza Vaccine. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a029496).</a>
3. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a029413.full.pdf+html" target="_blank">Sarah F. Andrews, et al. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Immunogenetic Considerations Underlying B-Cell Biology in the Development of a Pan-Subtype Influenza A Vaccine Targeting the Hemagglutinin Stem. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a029413).</a>
4. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a028845.full.pdf+html" target="_blank">Florian Krammer, et al. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Toward a Universal Influenza Virus Vaccine: Potential Target Antigens and Critical Aspects for Vaccine Development. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a028845).</a>
5. <a href="http://cshperspectives.cshlp.org/content/early/2017/06/29/cshperspect.a028852.long" target="_blank">Davide Angeletti and Johnathan W. Yewdell. (2017) Is it Possible to Develop a “Universal” Influenza Virus Vaccine? Outflanking Antibody Immunodominance on the Road to Universal Influenza Vaccination. Cold Spring Harbor Perspectives in Biology. (doi:10.1101/cshperspect.a028852).</a>
6. <a href="https://www.sciencedirect.com/science/article/pii/S0264410X16300822?via%3Dihub" target="_blank">Francesco Berlanda Scorza, et al. (2016) Universal Influenza Vaccines: Shifting to Better Vaccines. Vaccine. (doi:10.1016/j.vaccine.2016.03.085).</a>
7. <a href="https://www.sciencedirect.com/science/article/pii/S0264410X16307447?via%3Dihub" target="_blank">Erin Sparrow, et al. (2016) Passive Immunization for Influenza through Antibody Therapies, a review of the pipeline, challenges and potential applications. Vaccine. (doi:10.1016/j.vaccine.2016.08.057).</a>
___________________________ 1<a href="https://grandchallenges.org/video/grand-challenges-first-ten-years" target="_blank">Grand Challenges in Global Health – the First Ten Years</a> 2<a href="https://grandchallenges.org/video/grand-challenges-first-ten-years" target="_blank">Grand Challenges in Global Health – the First Ten Years</a> 3<a href="http://fortune.com/2018/03/21/universal-flu-vaccine/" target="_blank">Andrew Nusca, “Why We Need a Universal Flu Vaccine”, Fortune, 2018</a>

The Bill &amp; Melinda Gates Foundation and the Page Family are launching this grand challenge during the centenary year of the 1918 flu pandemic, with the goal of identifying novel, transformative concepts that would lead to development of a truly universal flu vaccine. Such a vaccine would alleviate the need for annual seasonal influenza vaccination campaigns and would prepare the world for the next influenza pandemic.

Challenges

Integrating Tradition and Technology for Fermented Foods for Maternal Nutrition

Smart Farming Innovations for Small-Scale Producers

Balance the Equation - A Grand Challenge for Algebra 1

Improving Access to and Use of Safe and Appropriate Cesarean Section

Accelerating Discovery for Non-Hormonal Contraceptives

2019 Grand Challenges Annual Meeting Call-to-Action

Voices for Economic Opportunity

Neglected Tropical Diseases Data Innovation Incubator

2018 Grand Challenges Annual Meeting Call-to-Action

Ending the Pandemic Threat: A Grand Challenge for Universal Influenza Vaccine Development

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Sign up for email updates of the latest grant opportunities and awards.

View the Grand Challenges partnership network

Great ideas come from everywhere.