Modeling the potential health impacts of delayed strain selection on influenza hospitalization and mortality with mRNA vaccines.

Background: Influenza viruses are constantly evolving through antigenic drift, which makes vaccines potentially ill-matched to circulating strains due to the time between strain selection and distribution. mRNA technology could improve vaccine effectiveness (VE) by reducing this time. Significant private and public investments would be required to accommodate accelerated vaccine development and approval. Hence, it is important to understand the potential impact of mRNA technology on influenza hospitalizations and mortality. Methods: We developed an age-stratified dynamic model of influenza transmission to evaluate the potential impact of increased VE (increased protection against either infection or only hospitalization) on hospitalizations and mortality in the United States. We assume that mRNA technology allows for delaying the time to strain choice, which might increase efficacy, but it does not reduce the time needed for distribution and administration, which might reduce availability. To assess this tradeoff, we evaluated two scenarios where strain choice was delayed until late summer resulting in a more effective vaccine available to (1) all age groups by October, or (2) adults 65 years and older starting in August. Results: If not available until October, the vaccine would need a minimum of 95% effectiveness against infection to see a decrease in hospitalizations and deaths in all age groups. When delayed until November, even a 100% effective vaccine had no significant impact. For the elderly, the minimum required VE (against infection) was 50% to reduce hospitalizations and deaths. Moreover, a vaccine with 80% VE against infection available in August for the 65 + age group was better than a 95% effective vaccine available in October for all ages. Conclusions: As the majority of influenza-associated hospitalizations and deaths are in adults 65 years and older, a combination policy targeting higher VE and coverage for this age group in the short term would be the most efficacious.