Large-Scale Immunity Profiling Sheds Light on Influenza Virus Evolution

Recent research has revealed that individual variations in antibody immunity significantly influence which influenza (flu) strains become predominant in populations. This groundbreaking study, published as a reviewed preprint in eLife, employed a high-throughput sequencing-based assay to analyze antibody responses against circulating H3N2 flu strains in both children and adults.

The researchers developed a robust, high-throughput neutralization assay capable of measuring how effectively blood serum samples can block infection by a diverse panel of flu viruses. They engineered 78 different viruses, each expressing unique hemagglutinin (HA) proteins from 2023 circulating strains and vaccine strains, with each virus tagged with a distinct genetic barcode. Using Illumina sequencing, they quantified the neutralizing capacity of sera collected from over 150 individuals—both children and adults—across the United States at the start of the 2023–2024 flu season, resulting in more than 11,000 detailed measurements.

Findings from the study showed notable diversity in immune responses among individuals. Some children displayed strong neutralization against nearly all tested strains, while others had a weaker response. Among adults, immune responses were more consistent but still varied considerably. Interestingly, children exhibited the highest neutralization responses for certain strains, possibly because early-life exposure heightens immunity to those viruses.

The team then linked these antibody response patterns to the viral strains' growth during the flu season through statistical modeling. They observed that strains capable of escaping neutralization—where many individuals had low antibody titers—had a higher likelihood of spreading successfully. This highlights that vaccine and surveillance efforts should consider individual immunity variations, as pooled serum samples may not fully capture the spectrum of immune responses.

The study underscores the importance of accounting for individual immune histories when predicting viral evolution. While the dataset has limitations due to a specific geographic and demographic focus, it represents one of the most extensive links between human antibody immunity and flu strain success to date. The methods demonstrated could support more precise vaccine development and improve surveillance by providing deeper insights into population immunity and viral adaptation.

Overall, this research advances our understanding of how diverse immune responses shape flu virus evolution and emphasizes the need for detailed, individual-level immunity assessments in public health strategies.

Source: https://medicalxpress.com/news/2025-06-large-scale-immunity-profiling-grants.html