Speaker
Description
Subclinical or asymptomatic influenza infections are likely to play a major role in ongoing transmission but require longitudinal cohorts to detect. The Household Influenza Vaccine Evaluation (HIVE) cohort is an ongoing study of households where participants respond to weekly symptom surveys and contribute biannual blood samples. From 2011 to 2020, 2039 participants contributed 8511 serum samples. This project aimed to design a library of up to 100 H3N2 and H1N1 viral strains for use in a high-throughput neutralization assay. By identifying the viral strains neutralised by each participant’s sera, we aimed to track infections over the study period, measure the quality of vaccine responses, and analyze how vaccinations and infections affect the viral epitopes targeted.
We downloaded all U.S. H3 (n=33,836) and H1 (n=16,483) hemagglutinin sequences from 2009 to 2023 from GISAID and calculated seasonal mutational frequencies. While 450/566 sites had at least one amino acid mutation, only 72 H3 sites and 59 H1 sites displayed mutations >5% within a season. After excluding solvent-inaccessible sites (10 for H3 and 8 for H1), 62 and 51 sites remained. 45 and 19 sites mapped to known H3 and H1 epitopes, and 17 and 3 were located at potential N-linked glycosylation sites.
We generated haplotypes across mutated sites, selected the most frequent haplotypes, and generated consensus sequences to represent them. This procedure resulted in a final library of 50 H3 and 26 H1 strains. The H3 library covers 88% of circulating H3 strains within one amino acid difference, while the H1 library covers 85% of circulating H1 strains. Our study demonstrates the feasibility of developing libraries that capture neutralizing antibody responses to a large fraction of circulating influenza A strains over nearly a decade, enabling detailed investigations of population and individual immune responses after diverse exposures.
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