Highly Pathogenic Avian Influenza Vaccines: challenges for innovation, technological development and pandemic preparedness

IntroductionHighly Pathogenic Avian Influenza (HPAI) pandemic potential is a critical issue. Outbreaks of H5N1 Avian Flu, causing mass die-offs in poultry and other birds, are now affecting mammals from otters to dolphins worldwide. H5N1 and other HPAI viruses have so far caused rare human infections. However, if they evolve to spread between people, they could trigger major outbreaks. The main question is: how to overcome bottlenecks in HPAI vaccine development to accelerate scale-up and implement an effective global Vaccine Preparedness System? MethodsFrom a patent landscape approach, we identified breakthroughs and gaps in HPAI vaccine development for the search period (2010-2021), discussing technological strategies in patent filings, including universal vaccine patent documents. ResultsVery few patent documents for human HPAI vaccines were retrieved: from 49 deposits in the search period, only 18 were in active status (37%), with few breakthroughs and in early stages of development. These results indicate a technological lag in HPAI vaccine development and highlight the constraints for scaling-up these vaccines when they will be needed. Current egg-based processes are laborious and too difficult to scale-up in the case of a pandemic. Concerning mRNA technology, there are still issues on the duration and level of protection mRNA vaccines might induce. Vaccinating farm animals is not sufficient to protect the population: if not properly executed, the virus could continue to circulate at a low level, increasing the chance of mutations and adaptation to humans. Universal Influenza vaccines would be key, but we identified only few (20 in the search period) patents for these vaccines, still in early stages of development. In addition, it is the impact immunological memory would have on the development of protective immunity to a broad-spectrum of viruses, due to original antigenic sin mechanism. DiscussionThis study identified critical barriers to overcome in HPAI vaccine development, improving efficacy and reducing costs. It highlights the urgent need for an effective global Vaccine Preparedness model, supported by Genomic, Antigenic and Epidemiological Surveillance, an Innovation Fund and Public-Private Partnerships. We strongly support WHO in coordinating a Global Initiative for Influenza Pandemic Preparedness.