Ending the Pandemic Threat: A Grand Challenge for Universal Influenza Vaccine Development
The Grand Challenge
(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
This is an all-hands-on-deck time. If we get there, we can make influenza history.3
Bruce Gellin, Sabin Vaccine Institute
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: Ending the Pandemic Threat: A Grand Challenge for Universal Influenza Vaccine Development.
To find a game changing, universal solution to all these challenges, the Bill & 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.
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:
- Engage scientists across a variety of disciplines, including those new to the influenza field
- Demonstrate innovative thinking by incorporating concepts or technologies not currently being used within/addressed by the influenza vaccine field
- Present concepts and strategies that are “off the beaten track,” significantly radical in conception, and daring in premise.
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:
- Antigen-centric: discovering new antigens/targets through Artificial Intelligence, Machine Learning, and/or Deep Learning approaches to get beyond traditional surface hemagglutinin
- 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
- 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
- Enabling advances: including challenge models to quickly demonstrate safety and proof-of-concept for influenza vaccines
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:
- Marginal improvements in current seasonal influenza vaccines
- Precedented approaches using biosimilars to antigens or adjuvants currently in clinical development
- Basic studies of pathogen or human biology without a clear component that tests the potential for translation into product
- Development of assays, new reagents, adjuvants, or production technologies improving licensed and late-stage vaccines already in development
- Therapeutic monoclonal antibodies for treatment of influenza patients.
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.
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.
2. 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).
3. 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).
4. 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).
5. 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).
7. 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).
1Grand Challenges in Global Health – the First Ten Years
2Grand Challenges in Global Health – the First Ten Years
3Andrew Nusca, “Why We Need a Universal Flu Vaccine”, Fortune, 2018