In study led by @ckikawa.bsky.social & Andrea Loes, we use new assay to measure ~10,000 neutralization titers to recent influenza strains & show titers correlate w evolutionary success of viral strains Similar data could help forecast evolution for vaccine selection biorxiv.org
www.biorxiv.org
As background, human seasonal influenza evolves to erode immunity. Vaccine updated regularly to keep pace w evolution, but forecasting which viral strains will dominate next season is hard. One limitation is we don’t fully understand human immune landscape that drives evolution. We recently developed high-throughput sequencing-based assay to measure how serum antibodies neutralize different influenza strains. With assay, we can measure 1,872 neutralization curves per 96-well plate, compared to traditional assays that yield 8 or 12 curves per plate.
We used this assay to measure neutralizing titers of a large set of >100 children and adult sera against a panel of viruses representing the H3N2 influenza diversity circulating in humans in 2023.
Different sera were better or worse at neutralizing different viral strains. Below plot shows a 14-year old child neutralized most strains but had lower titers to strains mutated at site 145; a 24-year old neutralized those strains well but had lower titers to other strains.
Below are titers of a large set of sera against all the strains. The plot shows the extensive heterogeneity of population antibody immunity: titers against different strains vary widely across individuals.
Can these measurements of antibody immunity across human population help us understand influenza evolution? To address that question, we worked w T Bedford, @huddlej.bsky.social, M Figgins, P Steinberg to estimate growth rates of different H3N2 strains in 2023 using multinomial logistic regression.
The actual growth rates of viral strains were highly correlated w fraction of sera w low titers to strains, as shown below. But there was no correlation if we just pooled all the sera and measured titers: per-serum measurements are needed to capture population heterogeneity.
We hope that high-throughput measurements of neutralization of many recent influenza strains by many human sera, which are feasible to make w these new methods, can help w efforts to forecast influenza evolution for vaccine strain selection. All data described above are at github.com Thanks to @ckikawa.bsky.social & Andrea Loes for leading study, w important contributions from @huddlej.bsky.social , M Figgins, P Steinberg, T Griffiths, E Troisi, Heidi Peck, Ian Barr, Jan Englund, @scottehensley.bsky.social, T Bedford
github.com
The final version of record of this study has been published in @elife.bsky.social alongside a nice insight perspective: elifesciences.org
elifesciences.org