The work was led by @ckikawa.bsky.social, Andrew Butler, and @huddlej.bsky.social. Thanks also to S Turner, H Peck, J Englund, K Lacombe, M Busch, M Lanteri, M Stone, B Spencer, A Greninger, D Smith, S Wallace, H Marshall, S Tosif, @scottehensley.bsky.social, & Ian Barr.

This is third installment of our efforts to generate near real-time data on human neutralizing antibody landscape to influenza. Our hope is that these data can improve vaccine-strain selection and ability to forecast short-term evolution of human seasonal influenza.

But effect of G155E mutation in H1N1 is highly variable across people. For most sera, strains with G155E have only mildly reduced neutralization---but some sera neutralize G155E strains much more poorly. Individuals who are strongly affected by G155E tend to be younger.

For H1N1, many new natural strains have modestly reduced neutralization by human sera relative to strain in 2026-2027 Northern Hemisphere vaccine. Strains w lowest neutralization often have G155E, which has emerged repeatedly in natural strains, especially in D.3.1.1 subclade.

We assembled set of 78 H3N2 and 62 H1N1 HAs from naturally occurring human seasonal strains that largely cover recent diversity of influenza circulating in human population. We measured neutralization of these viruses by 325 recent human sera.

We recently developed sequencing-based neutralization assays that measure how serum antibodies neutralize many viral strains. This enables us to measure in near real-time how new naturally emerging strains are neutralized by current human sera.

As background, human seasonal influenza evolves rapidly. HA protein of H3N2 influenza has accumulated >45 amino-acid mutations over last 18 years. This evolution erodes immunity, so vaccine updates considered twice per year (Sept & Feb for Southern & Northern hemisphere vaccines).