Awards

Lisa Rohan of the University of Pittsburgh in the U.S., with Thesla Palanee-Phillips of the Wits Health Consortium (Pty) Ltd in South Africa, will develop a vaginal film technology for the sustained release of the hormone levonorgestrel as a product that provides contraception and reduces heavy menstrual bleeding. Levonorgestrel is a progestin, a synthetic hormone that mimics the effects of progesterone. They will create and compare vaginal films with differences in mechanical properties, mucoadhesion, and drug release profiles to design a product that is low-cost, self-administered, and active for one month. They will also conduct a pilot trial of two prototype placebo films without levonorgestrel, evaluating them for safety, acceptability, and mucoadhesion in 20 women in South Africa, half with heavy menstrual bleeding.

Anne Beatrice Kihara with Moses Madadi, both of the University of Nairobi in Kenya, will pilot a multipronged approach to support research and development for women’s health in Kenya. They will co-develop a policy and regulatory framework that integrates gender equity, working with government stakeholders, including the Ministry of Health and regulators, as well as civil society groups and women-led organizations. They will develop case studies of healthcare technologies for women’s health, focused on how accessible these technologies are for women in underserved communities; launch community-based campaigns to increase awareness and understanding of women’s health and healthcare solutions; and train healthcare professionals in applying an equity perspective in women’s health research and care. Community feedback will guide an iterative approach throughout these efforts.

Mathew Njoroge of the University of Cape Town in South Africa, with Roslyn Thelingwani of the African Institute of Biomedical Science and Technology in Zimbabwe, will analyze liver tissue from an African patient biobank to characterize the variability in drug metabolism in African populations. The analysis will combine genotyping, in vitro physiology studies, and pharmacokinetic modeling. Using the biobank samples, they will perform targeted sequencing of genes known to be associated with drug absorption, distribution, metabolism, and excretion, and then use the genotyped samples for in vitro analysis of drug clearance. This data will be combined with data modeling to predict the variability of drug pharmacokinetics in vivo to guide drug development and inform the design, monitoring, and interpretation of clinical trials.

Cliveland Ogallo of the Center for Public Health and Development (CPHD) with Anne-Beatrice Kihara of the University of Nairobi, both in Kenya, will assess the impact of heavy menstrual bleeding on the health and well-being of adolescent girls in an underserved community in Kenya. Girls in the Kibera urban informal settlement will be surveyed, along with guardians and health workers, to assess the prevalence of self-reported heavy menstrual bleeding; menstrual health literacy and associated cultural narratives; hygiene practices; access to healthcare products and services; and impacts including anemia, school absenteeism, and psychosocial well-being. Small-scale interventions will also be piloted, such as introducing menstrual kits with educational packets and dedicated physical spaces for menstrual hygiene.

James Beeson of the Burnet Institute with Stephen Scally of The Walter and Eliza Hall Institute, both in Australia, will develop candidate malaria mRNA vaccines designed to confer multiple types of immunity over multiple lifecycle stages of the malaria parasite. They will start with lead candidates that target Plasmodium merozoites, screening them with a human organoid model of the germinal center for their ability to activate B cell responses. Based on these tests, they will add antigens and test the resulting multi-antigen vaccines in animal models to create candidates that confer anti-merozoite, anti-sporozoite, and transmission-blocking immunity.

Brian Sullivan of Arcturus Therapeutics, with Sean Murphy of the University of Washington Foundation, both in the U.S., will pilot test a self-amplifying mRNA vaccine technology as a platform for developing malaria vaccines. They will use a mouse model of malaria, establishing infections in parallel with two different Plasmodium parasite species. They will test preventive treatments in this model, comparing self-amplifying mRNA vaccine technology to conventional mRNA and comparing intramuscular versus intravenous administration. They will assess the ability of each test vaccine to protect against liver-stage infection, determining the number of liver-stage parasites and how well the vaccine elicits potent, malaria-specific T-cell responses in the liver. The prolonged antigen expression characteristic of self-amplifying mRNA vaccines could be particularly valuable in inducing long-term protection against malaria.

Sarah Leeber of the University of Antwerp in Belgium, with Marie Josiane Kenfack of the Center for Research on Emerging and Reemerging Diseases (CREMER) in Cameroon, will add DNA sequencing analysis of the vaginal microbiota as a component for a set of clinical trials of menstrual hygiene products in Belgium, Switzerland, Cameroon, and Peru. The longitudinal trials compare use of different menstrual products, with participants using either the same product over time or different products in sequence, including pads, tampons, cups, and underwear. Surveys and group discussions will be used to gather data on user perceptions of the products and how acquiring knowledge of the microbiome may influence attitudes and practices. Shotgun metagenomic sequencing from self-collected samples will reveal changes in the vaginal microbiota associated with different products. Together, this data will provide a more comprehensive understanding of both the biological and behavioral dimensions of menstrual product use.

Almaz Negash of the African Diaspora Network in the U.S. will build an AI-augmented collaboration hub that matches senior African scientists with experienced researchers and innovators in the African diaspora. The hub will include AI-assisted profiling of skills and needs, focusing on areas including pharmacogenetics, pharmaceutical manufacturing for preclinical and clinical trials, infectious disease control, and data science. The hub will host monthly masterclasses and peer-learning sessions, and it will support co-designed research, co-supervision of students, joint grant applications, and technology transfers. It will be launched with an inaugural cohort of Africa-based scientists, including the Calestous Juma Fellows as an existing network of science leaders already embedded in African universities and research centers.

Margaret Ilomuanya of the University of Lagos in Nigeria will develop a multifunctional microneedle patch for delivery of agents that treat heavy menstrual bleeding while preventing disease from sexually-transmitted viral infections. The patch will be designed for use on the abdomen or thigh, and it will have a layered architecture to deliver multiple drugs: tranexamic acid and the progesterone-mimic levonorgestrel to reduce bleeding (with levonorgestrel also having contraceptive activity) and the antiviral drug tenofovir. Microneedle-delivered tranexamic acid and levonorgestrel will be tested, both for their safety and their ability to control bleeding, in assays including clotting in vitro, a rat model, and a rabbit model of menstruation. Women experiencing heavy menstrual bleeding will be engaged for group discussions to assess the acceptability, usability, and desirability of the microneedle patch compared to existing treatment options, such as oral tranexamic acid and hormonal intrauterine devices.

Brandon DeKosky of the Massachusetts General Hospital, with Carole Long of the National Institute of Allergy and Infectious Diseases, both in the U.S., will develop a high-throughput, microfluidic screening platform to identify antibodies active against blood-stage malaria parasites. The platform is based on individual droplets containing a mix of Plasmodium parasite-infected and uninfected red blood cells together with mammalian cells secreting monoclonal antibodies. Each droplet serves as a parasite neutralization assay: antibodies that block parasite invasion of new red blood cells limit growth of the parasite population, and this is readily quantified using parasite-specific protein activity. With miniature droplets assayed in parallel, mammalian cells expressing a library of monoclonal antibodies can be rapidly screened for antimalarial activity.

Ianessa Morantte of Prolific Machines Inc. in the U.S. with Arif Jetha of Radiant Biotherapeutics Inc. in Canada, are combining complementary platforms to enhance the production of broadly neutralizing antibodies (bnAbs) against HIV. Radiant has developed the Multabody platform™, which uses a self-multimerizing scaffold to multimerize antibody fragments. These fragments will be expressed using Prolific's proprietary Photomolecular Biomanufacturing Platform, which leverages light-controlled (optogenetic) cell lines that provide tunable gene expression control, facilitating expression of complex biotherapeutics. Stable, optogenetic host cell lines will be engineered by Prolific Machines to express multimers, each with a different combination of antibody fragments. The system will be assessed for its ability to increase Multabody yields by separating growth and production, and provide control over antibody fragment ratios with light, with the goal to pursue scale-up at a cost low enough to broadly increase access.

Brandon Wilder with Daniel Streblow, both of Oregon Health and Science University in the U.S., will develop a vaccine platform based on virus-like vesicles (VLVs) as a vaccine vector that can be launched in vivo from nucleic acids and express proteins that elicit cellular and humoral immunity. They will optimize in vitro-generated VLVs for expression of an established Plasmodium berghei antigen and for immunogenicity in a mouse model of malaria. They will then vaccinate mice with gene gun-delivered, optimized plasmid DNA to demonstrate that VLVs can be generated in vivo, to assess their persistence and tissue distribution, and to test whether immunity can be boosted by a second vaccination.

Liya Wassie of the Armauer Hansen Research Institute in Ethiopia, with Richa Vashishtha of the Biotechnology Industry Research Assistance Council (BIRAC) in India, will develop resources for investigators in low- and middle-income countries (LMICs) to integrate ethical principles into the design and deployment of health-related AI technologies. They will establish and coordinate a multi-country AI ethics working group to develop a practical ethics guide for AI innovators, and the guide will be finalized through two public workshops. They will also launch public discussion sessions on key AI topics, such as algorithmic bias and data privacy, and coordinate an internship program on AI ethics for early- and mid-career LMIC investigators.

Moses Madadi of the University of Nairobi in Kenya, with Annettee Nakimuli of Makerere University in Uganda, will establish a platform for coordinated advocacy to reduce the burden of postpartum hemorrhage, a major cause of maternal mortality and morbidity. The platform will build on the inaugural advocacy meeting called Run for Her, which was held in Kenya in 2024. This meeting brought together an international group of healthcare practitioners, politicians, policy makers, students, and religious leaders to raise awareness about postpartum hemorrhage. They will establish an African continent-wide network, expanding from Kenya to ten additional African countries, with annual advocacy events to directly engage local communities and other key stakeholders. The platform will raise awareness and inform data-driven policies for procuring essential medications and therapies, training and reskilling healthcare workers, and establishing systems for ongoing data collection.

Atunga Nyachieo of the Kenya Institute of Primate Research (KIPRE) in Kenya, with Alfred Botchway of Attentive Science in the U.S., will perform a pilot study as a first step in creating an integrated, preclinical, toxicology testing hub at KIPRE to accelerate drug discovery. The pilot will begin with a toxicology study in rodents to assess existing protocols, including those for dose formulation, oral administration, observation and recording of clinical signs of toxicity, collection and processing of blood and tissue, and histopathology review of tissue slides. This assessment will identify gaps as well as guiding the development of standard operating procedures and of specialized training programs in toxicology and related disciplines.

Lyn-Marie Birkholtz with Erick Strauss, both of Stellenbosch University in South Africa, will develop antimalarial drugs that work by targeting parasite proteins for degradation rather than inhibiting their activity. This strategy involves creating proteolysis-targeting chimeras (PROTACs), which are linker proteins designed to bind specific parasite proteins and target them for degradation by an endogenous intracellular protease. This project builds on ongoing work with the approach applied to bacterial proteins for TB drug development. They will design and synthesize PROTACs against essential Plasmodium falciparum proteins, then evaluate their activity in phenotypic assays using drug-sensitive and drug-resistant parasite strains as well as multiple stages of parasite development. They will validate that any observed activity is due to the predicted PROTAC mechanism of action, as well as using in vitro assays to measure how effectively the parasites resist the antimalarial activity.

Garry Pairaudeau of DaltonTx Limited in the United Kingdom, with Gemma Turon of the Fundació Ersilia Open Source Initiative in Spain, will develop a computational platform for analyzing large, in silico, chemical libraries to identify chemical starting points for drugs that target Mycobacterium tuberculosis. They will use AI-based protein structure modeling focused on the several-hundred known proteins whose targeting can inhibit M. tuberculosis growth. They will incorporate information on ligand binding from available databases of chemical library screening experiments and the ChemBL database of bioactive molecules with drug-like properties. Together, this information will highlight the target proteins and the binding sites most likely to be amenable to in silico screening. This predictive modeling will be distilled and deployed through the Ersilia Model Hub platform as an open resource for virtual screening of compound libraries for tuberculosis drug discovery.

James Beeson of Burnet Institute in Australia, Melissa Kapulu of Health Research Operations Kenya Limited in Kenya, Isaac Ssewanyana of Infectious Diseases Research Collaboration in Uganda, Faith Osier of Imperial College London in the U.K. and Pras Jagannathan of Stanford University in the U.S., will analyze clinical samples using an antibody functional assay platform with malaria antigen arrays to identify antigens targeted by protective antibodies for next-generation malaria vaccines. They will identify antigen-specific functional antibodies that strongly correlate with protective immunity to malaria observed in clinical studies with two populations: Kenyan adults after controlled experimental challenge infection with Plasmodium falciparum and children followed longitudinally who were naturally exposed in Uganda and in Papua New Guinea. They will then use biostatistical modeling approaches to identify antigen and functional antibody types that most frequently occur in protective combinations, identifying additive and synergistic combinations of responses and responses most predictive of protective immunity across age groups and populations. This will enable prioritization of antigens and their combinations for malaria vaccine candidates.

Rajshekhar Karpoormath of the University of KwaZulu-Natal in South Africa will test a set of potential anti-TB hit compounds against clinically relevant TB strains, using the results to generate optimized hit compounds for development of new anti-TB drugs. They will screen the potential hits against susceptible, monodrug-resistant, multidrug-resistant, and extensively drug-resistant TB strains as well as other Mycobacterium strains. The screening results will inform structure-based drug design to generate optimized hit compounds. Potential lead hits will be screened again, with the most promising evaluated against intracellular bacteria in macrophages, tested for in vitro cytotoxicity, and evaluated for mechanism of action in bioassays including carbon-isotope tracing metabolomics and an in vitro granuloma assay.

Moses Obimbo Madadi of the University of Nairobi in Kenya and Aida Sivro of the University of Manitoba in Canada will determine the molecular epidemiology of human papillomavirus (HPV) in cervical cancer cases in Kenya to enable monitoring of changes in the prevalence of HPV types targeted by current vaccines and detect possible replacement with other types. They will perform a cross-sectional study on Kenyan women being followed-up for cervical cell abnormalities at hospitals in Nairobi and in rural Kenya. Outcome measures will include prevalence of HPV genotypes by age, geographic location, and HIV status. HPV genotypes will be stratified by cervical diagnosis to determine the top genotypes associated with cervical cancer. This research will provide robust and standardized statistics on the burden and genetics of oncogenic HPV infection in Kenyan women.

Wambui Nyabero of Medevice Kenya in Kenya and Vibhav Joshi of InnAccel Technologies Pvt Ltd in India will pilot test Fetal Lite, a fetal monitor for early detection of fetal distress to reduce intrapartum mortality. The monitor is designed for ease of use and patient comfort. It measures fetal and maternal heart rate and uterine activity, has automated data analysis with audio and visual alerts, and has a built-in electronic partogram and AI-based pregnancy risk scoring. It is cloud-enabled with a central web dashboard for report sharing and trend monitoring. They will deploy devices in medical facilities associated with the University of Nairobi, measuring the quality of the auto-generated analysis compared to blinded expert annotation and the ease of use by nursing staff. They will also capture the associated birth outcomes, the guidance provided through remote monitoring, and the number of detected fetal distress cases and referrals.

Daniel Muema of the KAVI Institute of Clinical Research, University of Nairobi in Kenya and Marit J. van Gils of the University of Amsterdam in the Netherlands will characterize the B cell immune repertoire in defined African populations to inform the use of an HIV vaccine with a germline-targeted immunogen. This clinically advanced, HIV envelope glycoprotein immunogen, BG505 SOSIP GT1.1, is engineered to guide the development of naïve B cells to produce broadly neutralizing antibodies (bnAbs) against HIV. They will determine the baseline frequencies of bnAb-precursor naïve B cells and bnAb-like memory B cells that recognize this immunogen in uninfected, adult sex workers highly exposed to HIV and in adults living with HIV. This will determine if the immunogen will be effective in these populations for HIV prophylaxis and functional cure, informing the design of vaccine clinical trials.

Seth Bloom of Massachusetts General Hospital and Margaret Kasaro of the University of North Carolina Global Projects Zambia in Zambia will validate metabolite biomarkers of clinically-relevant, vaginal microbiota community state types (CSTs) for development of diagnostics for research and clinical care. Different CSTs confer distinct risks for diseases linked to bacterial vaginosis, including risk of preterm birth and HIV infection. They will validate in a Zambian cohort the CST metabolite biomarkers that they previously identified in a South African cohort. They will grow pure cultures of individual bacteria to identify species and candidate enzymes responsible for vaginal CST biomarker production or consumption to inform development of a diagnostic assay. An inexpensive, real-time, point-of-care, diagnostic assay for use in low-resource settings would remove the need for slower, costlier DNA sequencing methods. Such a diagnostic test for vaginal microbiota-associated diseases will improve diagnosis, prediction of clinical risk, and monitoring of responses to therapy.

Digby Warner of the University of Cape Town in South Africa and Catherine Blish of Stanford University in the U.S. will explore human precision-cut lung slices (hPCLS) as an Mtb bioaerosol detection platform and model system for infection. Such a platform would provide an immediate read-out of Mtb infectivity and give insights into the initial Mtb-host interaction. They will determine the feasibility and reproducibility of using the hPCLS platform with samples containing extremely low numbers of Mtb bacilli, monitoring bacterial infectivity, replication, and dissemination by time-lapse fluorescence microscopy and examining key early events by cytometric and single-cell molecular assays. The platform could be used to answer specific questions, including whether Mtb organisms released during coughing by symptomatic TB patients are more infectious than those aerosolized during normal respiratory activities by asymptomatic individuals. It could also be applied at the site of aerosol sampling to guide and monitor preventative and therapeutic interventions.

Leon Tshilolo of the Institut de Recherche Biomédicale 1-Health in the Democratic Republic of Congo and Johnny Mahlangu of University of the Witwatersrand in South Africa will perform a pilot study using a mobile laboratory to conduct sickle cell disease (SCD) screening and patient follow-up in hard-to-reach and rural areas of the DRC. A mobile laboratory could lead to broader and earlier detection of SCD, enabling treatment sooner, and help ensure continued treatment, together reducing mortality and improving health outcomes. Sickle cell carriers will also be identified, with the study contributing to a more accurate epidemiological map of SCD to guide national healthcare strategy and advocacy efforts.

Erica Andersen-Nissen of Hutchinson Center Research Institute of South Africa and Gerhard Walzl of Stellenbosch University, both in South Africa, will perform bronchoalveolar lavage in volunteers receiving the BCG or MTBVAC vaccine intradermally in the HVTN 605 clinical trial to delineate vaccine-induced lung immune responses and identify correlates of protection. Lavage will be performed pre- and post-vaccination, and cells isolated from the lavage fluid will be analyzed for protein expression and by transcriptional profiling. They will compare the lung immune response they detect with the blood immune response identified in the large datasets available as part of the trial. Correlations between them could identify human blood biomarkers of lung T-cell responses that protect against TB. Such biomarkers will inform ongoing and future studies of immune correlates of efficacious TB vaccines.

Rajeev Shrestha of Dhulikhel Hospital Kathmandu University Hospital in Nepal with the Institute of Tropical Medicine Antwerp in Brussels and Paul Pronyk of National University of Singapore in Singapore will establish an integrated surveillance platform to speed the detection of dengue and the response to dengue outbreaks in Nepal. The platform will encompass dengue surveillance at multiple levels. Ecological and community-based surveillance will incorporate population-based, longitudinal dengue serosurveys to identify dengue hotspots. Hotspot mapping will integrate meteorological data for targeted mosquito vector surveillance, including serotype-specific detection of dengue virus in mosquitoes. Hospital-based surveillance will combine PCR-based dengue detection with information on clinical outcomes at sites across diverse geographical locations in Nepal, and genomic profiling will be performed for a subset of these circulating dengue strains. The integrated platform will serve national health authorities and policymakers, while setting the stage for similar platforms targeting additional emerging infectious diseases.

Jo-Ann Passmore of the University of Cape Town in South Africa and Elizabeth Bukusi of KEMRI in Kenya will determine the effects of the antibiotic metronidazole on bacterial vaginosis (BV)-associated microbes to guide the development of a live biotherapeutic product (LBP). BV is treated with antibiotics like metronidazole (MTZ), but recurrence is high, and an LBP could sustainably interrupt BV. They will compare temporal changes in abundance of BV-associated bacteria in women from Kenya and South Africa receiving MTZ treatment, and they will evaluate the impact of MTZ treatment on cervicovaginal inflammatory profiles. They will also compare antibiotic resistance prevalence and profiles for BV-associated bacterial strains isolated from these women, before and after MTZ treatment. The results will guide the interpretation of ongoing and future LBP efficacy studies, as well as generating a panel of BV-associated bacterial strains that can be screened to help select new candidate LBP strains.

George Wamukoya of African Group of Negotiators Experts Support (AGNES) in Kenya and Seyram Agbemenya of Africa Capacity Building Foundation in Ghana will establish an African hub of technical support for country teams to develop proposals for climate change adaptation projects fundable by the public and private sectors and philanthropies. They will pilot the approach through proposal writing workshops bringing together teams across at least three countries. The teams will include experts from the government, private sector, and academia. Together, they will profile the risks as described in the climate policy documents for their respective countries to build a business case, while analyzing the international climate finance landscape to identify aligned funding opportunities. They will take a portfolio approach to identify a strategic pipeline of projects to accelerate climate change adaption in Africa.

Jacqueline Weyer of the National Institute for Communicable Diseases in South Africa and Jinal Bhiman of Wits Health Consortium (Pty) Ltd also in South Africa will leverage a rapid monoclonal antibody (mAb) isolation and screening pipeline to develop diagnostics that differentiate between pathogens to support epidemic responses. Africa’s burden of many zoonoses and vector-borne diseases (VBD), such as Lassa fever and yellow fever, remains largely unknown, mainly due to diagnostic costs and limited access to reagents. They will leverage an existing screening pipeline, with infrastructure established by the Global Immunology and Immune Sequencing for Epidemic Response - South Africa (GIISER-SA) project, using a mouse model as a more readily available source of pathogen-specific B cells to identify mAbs that detect three ebolavirus species. These mAbs will be tested for sensitivity and specificity using patient samples and can be used to develop immunoassays, including rapid lateral flow assays, which are important for rapid, field-based diagnosis.

Anne Lee of Brigham and Women's Hospital in the U.S. and Yasir Shafiq of Aga Khan University in Pakistan will develop geospatial models to predict risks of undernutrition among adolescent girls and pregnant and lactating women in settings affected by conflict, climate and COVID-19 to help target interventions. Globally, around 30–40 million pregnant women and 50 million adolescent girls are underweight. Risks of undernutrition have recently been amplified by numerous armed conflicts, climatic shocks such as flooding and the COVID-19 pandemic. However, real-time data shortages prevent interventions, such as balanced energy-protein supplements, from reaching the highest-risk groups. Using Bayesian Hierarchical Spatial modeling, they will develop geospatial models for countries vulnerable to conflict and climate change, such as Ethiopia and Yemen. By incorporating socio-demographic and economic indicators, and climate-related and conflict-related shocks from national databases, they can estimate risks based on exposure and predict outcomes, such as undernutrition and anemia.

Margaret Kasaro and Soumya Benhabbour of the University of North Carolina at Chapel Hill in the U.S. will evaluate 3D-printed intravaginal ring (IVR) prototypes in Zambia to identify the design most acceptable to women for long-term use against unplanned pregnancy and HIV infection. In Zambia, HIV prevalence remains particularly high among women, and 41% of pregnancies are unplanned. IVRs are an effective, well-tolerated, and women-controlled contraceptive and HIV-preventative; however, their performance has suffered in large-scale clinical trials because of poor adherence. They have exploited a state-of-the-art 3D-printing process to rapidly engineer IVRs in a cost-effective, single-step process enabling the controlled release of multiple drugs for HIV prevention and contraception. They will recruit around 16 women, aged 18–45 from Kampala Health Centre, and use focus groups to evaluate their views on the proposed 90-day timeframe of use for four different IVR prototypes to guide the final design.

Yasir Shafiq of Aga Khan University in Pakistan and Anne Lee of Brigham and Women's Hospital in the U.S. will develop geospatial models to predict risks of undernutrition among adolescent girls and pregnant and lactating women in settings affected by conflict, climate and COVID-19 to help target interventions. Globally, around 30–40 million pregnant women and 50 million adolescent girls are underweight. Risks of undernutrition have recently been amplified by numerous armed conflicts, climatic shocks such as flooding and the COVID-19 pandemic. However, real-time data shortages prevent interventions, such as balanced energy-protein supplements, from reaching the highest-risk groups. Using Bayesian Hierarchical Spatial modeling, they will develop geospatial models for countries vulnerable to conflict and climate change, such as Ethiopia and Yemen. By incorporating socio-demographic and economic indicators, and climate-related and conflict-related shocks from national databases, they can estimate risks based on exposure and predict outcomes, such as undernutrition and anemia.

Raghavan Varadarajan in collaboration with Sudha Kumari, both of the Indian Institute of Science in India and Nico Callewaert of the VIB-UGent Center for Medical Biotechnology in Belgium will modify the microorganism, Pichia pastoris, used to produce lower-cost vaccines in low-resource settings, to generate more effective vaccines. Many vaccines are composed of pathogen-derived proteins that require production inside other cells. Although P. pastoris can produce these antigens at a lower cost than mammalian or insect cells, the viral proteins it produced for the SARS-CoV-2 vaccine were hyperglycosylated and poorly immunogenic, unlike those produced in mammalian cells. They will express different antigen forms in mammalian cells, and in different Pichia hosts, to determine whether altering glycosylation and protein size affects immunogenicity. They will also glycoengineer Pichia hosts to determine whether they can produce more effective vaccines. Ultimately, this approach could improve vaccine production for COVID-19 and other viruses.

Jinal Bhiman of Wits Health Consortium (Pty) Limited in South Africa and Jacqueline Weyer of the National Institute for Communicable Diseases also in South Africa will leverage a rapid monoclonal antibody (mAb) isolation and screening pipeline to develop diagnostics that differentiate between pathogens to support epidemic responses. Africa's burden of many zoonoses and vector-borne diseases (VBD), such as Lassa fever and yellow fever, remains largely unknown, mainly due to diagnostic costs and limited access to reagents. They will leverage an existing screening pipeline, with infrastructure established by the Global Immunology and Immune Sequencing for Epidemic Response - South Africa (GIISER-SA) project, using a mouse model as a more readily available source of pathogen-specific B cells to identify mAbs that detect three ebolavirus species. These mAbs will be tested for sensitivity and specificity using patient samples and can be used to develop immunoassays, including rapid lateral flow assays, which are important for rapid, field-based diagnosis.

Simon Kariuki of the Liverpool School of Tropical Medicine, Kenya in Kenya and Holden Maecker of Stanford University in the U.S. will determine whether probiotics and synbiotics can boost infant immune responses to vaccines. Diarrhea is the second leading cause of death in young children, with rotavirus a leading culprit. Oral rotavirus vaccines are routinely administered in low- and middle-income countries (LMIC) but are only 50% effective compared to 85–98% effectivity in high-income countries. One major cause could be environmental enteric dysfunction (EED), which is pervasive in children in LMIC. Their clinical trial of 600 newborns from western Kenya indicated that administering weekly probiotics and synbiotics (Lactobacilli and Bifidobacteria) up to age six months improved gut health and prevented EED-associated inflammation. They will use stored plasma samples and vaccination records to determine the impact of EED and systemic inflammation, as well as pro- and synbiotic effects on rotavirus vaccine efficacy.

Georgia Tomaras and Nathanial Chapman of Duke University and Girija Goyal and Don Ingber of the Wyss Institute at Harvard University, both in the U.S., will test whether Organ-on-a-Chip technology can inform how antibodies protect humans from pathogen infections to design more effective vaccines. Identifying protective vaccine features and validating them in human clinical trials is time-consuming and costly. An alternative is to use primary human organ chips that reproduce human physiology in vitro. They will stimulate peripheral blood mononuclear cells on the human lymph-node-on-a-chip with existing COVID vaccines and extensively characterize the resultant antibodies, including evaluating epitope specificity, and isotype and glycan profiling. They will also assess the capacity of these antibodies to prevent or reduce SARS-CoV-2 infection using the lung-on-a-chip technology. This approach can ultimately be applied to other pathogens, such as those causing malaria.

Cameron Myhrvold of Princeton University and Mireille Kamariza of the University of California, Los Angeles, both in the U.S., will develop an assay to rapidly detect multiple drug resistance mutations in Plasmodium falciparum and Mycobacterium tuberculosis for malaria and tuberculosis (TB) surveillance, respectively. Malaria and TB are two of the world's deadliest infectious diseases. Rapid and accurate drug resistance testing can save lives but current assays are slow or difficult to scale. Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN) is a CRISPR-based diagnostic test that detects nucleic acid biomarkers, such as those in pathogens, with high specificity and throughput. They have developed microfluidic CARMEN (mCARMEN), which produces results in under five hours, and will use an algorithm to design assays that detect the top ten drug-resistant P. falciparum mutations from blood samples, and M. tuberculosis mutations from saliva samples that confer resistance to two first-line TB drugs.

Maurício Barreto and colleagues of Fiocruz in Brazil, together with Alexa Heeks and colleagues of the Health Foundation of South Africa in South Africa, will employ real-world data from two large countries of the Global South to develop a common data model of infectious diseases affecting pregnant women to identify causes and aid intervention development. Centro de Integração de Dados e Conhecimentos para Saúde (CIDACS), together with the Western Cape Provincial Health Data Centre (WCPHDC), have built data systems to utilize routinely collected health data for exploring disease impacts. They will leverage these data systems to explore the impact of gestational syphilis in Bahia, Brazil, and tuberculosis in the Western Cape province of South Africa, and the coverage and effects of screening interventions. Teams will include data curators, analysts and scientists, who will perform data discovery and processing, alongside epidemiologists, clinicians and public health specialists, who will perform epidemiological analyses and community engagements.

Alexa Heeks and colleagues of the Health Foundation of South Africa in South Africa, together with Maurício Barreto and colleagues of Fiocruz in Brazil, will employ real-world data from two large countries of the Global South to develop a common data model of infectious diseases affecting pregnant women to identify causes and aid intervention development. Centro de Integração de Dados e Conhecimentos para Saúde (CIDACS), together with the Western Cape Provincial Health Data Centre (WCPHDC), have built data systems to utilize routinely collected health data for exploring disease impacts. They will leverage these data systems to explore the impact of gestational syphilis in Bahia, Brazil, and tuberculosis in the Western Cape province of South Africa, and the coverage and effects of screening interventions. Teams will include data curators, analysts and scientists, who will perform data discovery and processing, alongside epidemiologists, clinicians and public health specialists, who will perform epidemiological analyses and community engagements.

Seth Adu-Afarwuah of the University of Ghana in Ghana and Julie Croff of Oklahoma State University Center for Health Sciences in the U.S. will assess the effects of nutritional supplementation on adolescent brain development in low-resource settings to support interventions. Nutritional behavior majorly impacts the rapid stage of adolescent neurodevelopment, which in turn impacts future generations through effects on maternal and paternal nutritional status, cognition and parenting. However, little is known about typical adolescent neurodevelopment in low- and middle-income countries, where 90% of the world’s adolescents live. They will recruit 40–60 post-pubertal adolescents in Accra, Ghana, measure their corticolimbic system development over nine months, and assess their problem-solving, planning and cognitive functioning. In another cohort of 40–60 post-pubertal adolescents, they will measure adherence to an eight-month twice-daily micronutrient supplementation program and associated nutritional outcomes.

Julie Croff of Oklahoma State University Center for Health Sciences in the U.S. and Seth Adu-Afarwuah of the University of Ghana in Ghana will assess the effects of nutritional supplementation on adolescent brain development in low-resource settings to support interventions. Nutritional behavior majorly impacts the rapid stage of adolescent neurodevelopment, which in turn impacts future generations through effects on maternal and paternal nutritional status, cognition and parenting. However, little is known about typical adolescent neurodevelopment in low- and middle-income countries, where 90% of the world’s adolescents live. They will recruit 40–60 post-pubertal adolescents in Accra, Ghana, measure their corticolimbic system development over nine months, and assess their problem-solving, planning and cognitive functioning. In another cohort of 40–60 post-pubertal adolescents, they will measure adherence to an eight-month twice-daily micronutrient supplementation program and associated nutritional outcomes.

Brigida Rusconi of Washington University in the U.S. will determine whether female infants develop long-lived antibodies against gut bacteria that subsequently both protect against bacterial infections and promote healthy gut immune and microbiota development in their offspring. Enteric bacterial infections are leading causes of infant morbidity in low- and middle-income countries. Using their mouse model, they found that mothers lacking IgG antibodies, which normally develop before weaning, are unable to provide passive protection against enteric infections to their pups. They will adapt their microbial flow cytometry to test whether maternal serum IgGs react more strongly to infant gut bacteria, suggesting establishment in infancy, and whether they provide passive immunity during pregnancy. They will also analyze plasma from two-year-old infants to identify those with weak IgG reactivity and potential causes. Finally, using a malnutrition cohort in Pakistan, they will train local bioinformaticians and assess whether malnutrition inhibits anti-gut commensal IgG responses.

Daniel Kiboi of the Jomo Kenyatta University of Agriculture and Technology in Kenya will assess whether a novel mutation in the human malaria parasite, Plasmodium falciparum, can be used as a marker to identify drug-resistant malaria and protect key antimalarial drugs. Emerging P. falciparum variants resistant to the three frontline drugs kill millions of people annually but are hard to detect. A better understanding of how these variants resist the actions of existing drugs can help to develop more effective drugs. They previously used a mouse malaria model to produce Plasmodium parasites resistant to all three main drugs and identified the candidate mutated protein likely causing this resistance. They will use in silico bioinformatics analysis, CRISPR/Cas9 approaches, and in vitro drug susceptibility assays to evaluate and validate this mutant protein and determine its role in drug resistance in the human malaria parasite.

Yingda Xie of Rutgers New Jersey Medical School in the U.S. and Joaniter Nankabirwa of Makerere University in Uganda will use CRISPR-based technology to monitor respiratory, food-borne and antimicrobial-resistant pathogens in Ugandan wastewater. A recent Ebola outbreak in Uganda highlights the need for routine multi-pathogen surveillance. However, the vast quantities and diversities of microbes in wastewater make it hard to identify those that might cause deadly outbreaks. They will combine CRISPR-based diagnostics with the recently developed multiplex assay, Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), which enables highly sensitive and specific detection of over 150 nucleic acid sequences from dozens of samples in parallel. They will assess the performance of a field-deployable CRISPR assay to monitor specific pathogens in hospital sewage lines of Mulago Hospital. They will also leverage CARMEN to broadly survey for high-priority outbreak pathogens, including Ebola and yellow fever, in Kampala’s regional wastewater sources.

Carl Lachat of Ghent University in Belgium and Firehiwot Workneh of Addis Continental Institute of Public Health in Ethiopia will assess nutrient gaps in adolescent girls and the feasibility of providing supplements to break intergenerational cycles of poor growth and development in Burkina Faso and Ethiopia. Annually, around 21 million adolescent girls in low- and middle-income countries become mothers, with their infants at increased risk of impaired development. This may be caused by nutrient competition as both pregnancy and adolescence are nutrient-demanding phases. Supplementation with balanced energy-protein (BEP) during pregnancy increases birth weight with sustained benefits during infancy, but how this intervention could be tailored to adolescent girls is unclear. They will use a probability of adequacy approach to evaluate the diets and nutrition of 200 adolescent girls. They will also assess adolescent girls’ acceptability of paying for and taking BEP supplements in rural settings using group discussions and questionnaires.

Herman Pontzer of Duke University in the U.S. and Patricia Ukegbu of the Michael Okpara University of Agriculture in Nigeria will track the daily energy expenditures and requirements, and nutritional statuses of adolescent girls in rural Nigeria to help support their growth and development. Low- and middle-income countries suffer greatly from undernutrition, poor dietary practices and food insecurities, but are also experiencing increased obesity and unhealthy weight gain. Adolescents are particularly vulnerable to poor nutritional health but often neglected in nutritional program planning due to a lack of accurate data. To address this, they will recruit fifty female adolescents aged 13–18 from selected urban and rural schools in Abia State and measure their daily energy expenditure (kcal/d) and body composition (fat%) using the gold-standard doubly-labeled water method. This will be combined with dietary, food security and physical activity assessments to develop an accurate evaluation of nutritional health.

Kathryn Holt of the London School of Hygiene and Tropical Medicine in the United Kingdom and Senjuti Saha of the Child Health Research Foundation (CHRF) in Bangladesh, along with FTIR experts Luísa Peixe and Angela Novais from the University of Porto, will establish Fourier-Transform infrared (FTIR) spectroscopy in a pediatric microbiological diagnostics laboratory in Bangladesh to support clinical and infection control decisions. FTIR is a relatively low-cost, reagent-free technique that can discern different pathogen strains when combined with attenuated total reflection (ATR). They will set up a Spectrum Two FTIR-ATR instrument, on loan from PerkinElmer at the CHRF, train personnel, and use it to acquire spectra from approximately 1,500 isolates from their biobank to identify three clinically important pathogens: Klebsiella, Acinetobacter, and Salmonella. They will assess reproducibility across different users and laboratories on a validation set of 100 sequenced isolates, and finally test whether FTIR can identify pathogens directly in blood to produce more rapid results.

Rose Hayeshi of North-West University in South Africa will test whether humanized mouse models harboring selected gene variants specific to indigenous African populations can be used to identify novel therapeutics that will be effective in this population before advancing into clinical trials. Most medicines are developed and tested in European and Asian populations, which can lead to approved drugs that cause adverse reactions or are ineffective in African populations. Cytochrome P450 (CYP) enzyme allelic variants are common in African populations and may affect drug responses. She will use humanized mouse models expressing CYP2B6 and the CYP2B6*6 allelic variant, which is common in African populations, to test whether they can recapitulate specific drug responses observed in vitro and in humans using physiologically-based pharmacokinetic (PBPK) modeling.

Marion Jourdan of Danone Nutricia Research in the Netherlands together with Michael Zimmermann of ETH Zürich in Switzerland will test an approach to enhance iron absorption from food in children in Kenya by providing them with live food-grade bacteria to release phytate-bound iron from popular foods such as cereal flour. Phytates bind strongly to iron and inhibit its absorption. Their previous work identified different bacterial strains containing phytases that could grow in milk, degrade phytates, and release nutritionally-relevant levels of free iron in vitro. They will test different strain combinations for their phytate-degrading activity under different conditions, such as in specific foods and in an environment mimicking the upper GI tract, and select the best one for producing a fermented food product. This will then be tested to assess its effect on iron absorption in a cohort of 22 iron-deficient Kenyan school-aged children.