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Bloom lab
Bloom lab

We have posted data providing real-time measurement of human neutralizing antibody landscape to seasonal influenza. Data explain spread of subclades K (H3N2) & D.3.1.1 (H1N1), identify subclade K subvariants w reduced neutralization, & can inform choice of strains for next vaccine.

We used sequencing-based neutralization assays, which measure neutralization of 100s of viruses at once. One grad student @ckikawa.bsky.social measured ~27,000 neutralization curves in ~2 months, w many collaborators sharing sera & helping w analysis See preprint: biorxiv.org

https://www.biorxiv.org/content/10.6

www.biorxiv.org

Specifically, we first assembled a set of 57 H3N2 and 34 H1N1 strains that largely cover the current diversity of human seasonal influenza (see image below). We then measured neutralization of all 91 strains against 302 sera from humans of a range of ages (0 to 103 years) and geographic locations.

Resulting datasets are very rich. Below are H3N2 data (also under first post in this thread). There is extreme variability among human sera; the median serum has ~1.5-2-fold lower neutralization of subclade K. See jbloomlab.github.io to explore interactive plot

Our finding of ~1.5-2-fold lower median titers to subclade K concurs w recent studies by: @scottehensley.bsky.social - doi.org Barouch lab - doi.org @prmurcia.bsky.social - doi.org Skowronski lab - pubmed.ncbi.nlm.nih.gov

Antibodies elicited by the 2025-2026 influenza vaccine in humans

doi.org

Probably because of these lower titers, subclade K has rapidly become dominant among H3N2, rising from <1% to 95% frequency in ~9 months. See below image from this Nextstrain link (nextstrain.org).

For vaccine update decisions, we care about what is NEXT. Here our data help by showing that within subclade K strains there are already new subvariants w further reduced neutralization. These subvariants have additional mutations as shown below & interactively at nextstrain.org

The mutations that further reduce neutralization of subclade K are in antigenic regions D & E, which were less mutated in parent subclade K See below from recent @scottehensley.bsky.social preprint (doi.org) & stay tuned for study from their group that explains this observation

For H1N1 influenza, a new subclade (D.3.1.1) has also recently spread to become dominant, and our data show that this new subclade has reduced neutralization by human sera See jbloomlab.github.io for interactive version of below plot

So both H3N2 & H1N1 subclades that recently spread have reduced neutralization. But median titer drop to subclade K (H3N2) and D.3.1.1 (H1N1) only ~1.5-2 fold across 302 human sera. Relative to SARS-CoV-2 variants in 2021-2022, this seems like small titer drop. But types of variants we saw early in COVID-19 pandemic (eg, Omicron w ~10-fold titer drop) are not norm for endemic viruses. H3N2 subclade K shows “only” a ~1.5-2-fold titer drop is enough for variant to spread rapidly & cause worse-than normal influenza season. Of course, lots of people still have good titers to subclade K---and most people didn’t get influenza this year. But for seasonal vaccines we’d like to identify variants like subclade K which, although not pandemic scale, still make for a bad flu season. The large neutralization dataset described above provides resolution that can help achieve this goal and inform better vaccine-strain selection. All data are publicly available at github.com Please explore the visualizations or download them for further analysis!

GitHub - jbloomlab/flu-seqneut-2025to2026: Near real-time data on the human neutralizing antibody landscape to influenza virus as of early 2026 to inform vaccine-strain selection

github.com

I’d also like to note that @ckikawa.bsky.social was recently given a Beyond the Journal Award for the way she has been sharing these and similar data on GitHub in real-time as they are generated: experiment.foundation

Beyond the Journal Awards — Experiment Foundation

www.experiment.foundation

Thanks to all our collaborators: @huddlej.bsky.social, S Turner, A Loes, J Liu, S Gang, T Griffiths, @troisie.bsky.social, B Cowling, F Ho, N Leung, J Englund, K Lacombe, S Watanabe, H Hasegawa, M Busch, M Lanteri, M Stone, B Spencer, @neher.io, D Smith, T Bedford, @scottehensley.bsky.social Also thanks to @ceirrnetwork.bsky.social, @niaidnews.bsky.social, and @hhmi-science.bsky.social for support.

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