Abstract
Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neutralization titers for 78 recent H3N2 HA strains against a large set of children and adult sera, measuring ~10,000 total titers. There is substantial person-to-person heterogeneity in the titers against different viral strains, both within and across age cohorts. The growth rates of H3N2 strains in the human population in 2023 are highly correlated with the fraction of sera with low titers against each strain. Notably, strain growth rates are less correlated with neutralization titers against pools of human sera, demonstrating the importance of population heterogeneity in shaping viral evolution. Overall, these results suggest that high-throughput neutralization measurements of human sera against many different viral strains can help explain the evolution of human influenza.
Competing Interest Statement
JDB is on the scientific advisory boards of Apriori Bio, Invivyd, Aerium Therapeutics, and the Vaccine Company. JDB consults for GlaxoSmithKline and Pfizer. JDB and ANL receive royalty payments as inventors on Fred Hutch licensed patents related to incorporating barcodes into the influenza genome and viral deep mutational scanning. SEH is a co-inventor on patents that describe the use of nucleoside-modified mRNA as a vaccine platform. SEH reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck.
