Collaborators: Cécile Viboud (NIH) , John Huddleston (Fred Hutch) , Trevor Bedford (Fred Hutch) , Florian Krammer (Mt. Sinai) , WHO Global Influenza Surveillance and Response System (GISRS) Collaborating Centers in Atlanta, London, Melbourne, and Tokyo
Influenza viruses continually accumulate genetic changes in epitopes of two major surface proteins, hemagglutinin (HA) and neuraminidase (NA), in a process called “antigenic drift.” Antigenic drift enables flu viruses to evade immune recognition, leaving previously exposed individuals susceptible to reinfection and requiring regular updates to the flu vaccine. Antigenic drift is expected to increase host susceptibility, leading to more flu cases and in turn earlier, larger, or more severe epidemics. However, epidemiological evidence for the impact of antigenic evolution on seasonal flu outbreaks is conflicting.
In a recent eLife article, we compared experimental and sequence-based measures of A(H3N2) virus evolution in predicting regional epidemic dynamics in the U.S. across 22 flu seasons (1997-2019), while also accounting for the co-circulation of other flu types/subtypes, prior population immunity, and vaccination (Perofsky et al. 2024 ). We found that evolution in both major surface proteins contributes to variability in epidemic magnitude across seasons, although viral evolution appears to be secondary to subtype interference in shaping annual outbreaks. When comparing the predictive performance of different evolutionary indicators, genetic changes in broad sets of epitope sites had stronger, more consistent relationships with A(H3N2) epidemic dynamics than the serological assays traditionally used to measure antigenic changes. As an extension of this work, we are exploring the impacts of antigenic drift, prior population immunity, and egg-adaptive mutations on A(H3N2) vaccine effectiveness in the U.S.
Collaborators: Martha Nelson (NIH) and Andrew Bowman’s group (Ohio State)
Each summer in the U.S., youths attending agricultural fairs are exposed to genetically diverse influenza A viruses (IAVs) circulating in exhibition swine, leading to hundreds of zoonotic infections since 2010. Exhibition swine, comprising 1.5% of the U.S. herd, present a targeted opportunity to mitigate a pandemic threat. We analyzed virologic surveillance data from thousands of pigs at 350 national, state, and local swine exhibitions across several states during 2016–2018.
Key findings: