A Grand Challenge for Universal Influenza Vaccine Development

BACKGROUND

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.

OBJECTIVES

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.