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J Virol . Strain-specific differences in the response to egg-derived versus recombinant protein influenza vaccines

tetano

Editor, Senior Moderator
J Virol


. 2026 May 27:e0031726.
doi: 10.1128/jvi.00317-26. Online ahead of print.
Strain-specific differences in the response to egg-derived versus recombinant protein influenza vaccines

Andrea N Loes[SUP] 1 2 [/SUP], Rosario Araceli L Tarabi[SUP] 2 [/SUP], Shuk Hang Li[SUP] 3 [/SUP], Reilly K Atkinson[SUP] 3 [/SUP], John Huddleston[SUP] 4 [/SUP], Caroline Kikawa[SUP] 2 5 6 [/SUP], Tachianna Griffiths[SUP] 3 [/SUP], Elizabeth M Drapeau[SUP] 3 [/SUP], Sook-San Wong[SUP] 7 [/SUP], Samuel M S Cheng[SUP] 7 [/SUP], Nancy H L Leung[SUP] 7 [/SUP], Sarah Cobey[SUP] 8 [/SUP], Benjamin J Cowling[SUP] 7 [/SUP], Trevor Bedford[SUP] 1 4 [/SUP], Scott E Hensley[SUP] 3 [/SUP], Jesse D Bloom[SUP] 1 2 [/SUP]


Affiliations
Abstract

The 2023/2024 influenza vaccine included an updated H1N1 component designed to better match a new clade of H1N1 that had multiple mutations in antigenic epitopes of hemagglutinin. Despite this update, the vaccine trended toward being less effective against the vaccine-matched H1N1 clade than the parental H1N1 clade lacking the new antigenic mutations. Here, we measure neutralization titers of serum antibodies from individuals who had received either a recombinant protein or an egg-derived vaccine against a set of viruses with hemagglutinins from 58 H1N1 strains representative of the diversity during the 2023/2024 season. We find that egg-derived vaccine recipients, but not recombinant protein vaccine recipients, had a relatively lower boost in neutralizing titers to the new clade that the updated vaccine was designed to target. We suggest that the difference in the extent that the egg-derived vs recombinant protein vaccines boosted neutralizing titers to the new H1N1 clade is because the seed strain for the egg-derived vaccine strain had acquired a reversion of a key antigenic mutation (K142R) present in that clade. Our results show how egg-derived vs recombinant protein vaccines can elicit different relative titer boosts against different subsets of viral strains, a phenomenon that could impact vaccine effectiveness.
Importance: Influenza vaccines can be produced from virus grown in eggs or grown in cells or made with recombinant protein. Egg-derived influenza vaccines often contain egg-adaptive mutations in the viral antigen hemagglutinin (HA) which can impact the antigenicity or immunogenicity of the HA. In this study, we compare neutralization titers from egg-derived and recombinant protein vaccine recipients against recently circulating influenza A(H1N1) strains. We find that the egg-derived vaccine induces less of a boost in titers than the recombinant protein vaccine to the new clade of viral strains that the vaccine was designed to target.

Keywords: egg adaptation; hemagglutinin; influenza; influenza vaccine; pdmH1N1; sequencing-based neutralization assay.

 
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