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

Loes, A. N.; Tarabi, R. A.; Li, S. H.; Atkinson, R. K.; Huddleston, J.; Kikawa, C.; Griffths, T.; Drapeau, E. M.; Wong, S.-S.; Cheng, S. M.; Leung, N. H.; Cobey, S.; Cowling, B. J.; Bedford, T.; Hensley, S. E.; Bloom, J. D.

doi:10.64898/2026.02.23.707528

bioRxiv · 10.64898/2026.02.23.707528

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

Loes, A. N.·Tarabi, R. A.·Li, S. H.·Atkinson, R. K.·Huddleston, J.·Kikawa, C.·Griffths, T.·Drapeau, E. M.·Wong, S.-S.·Cheng, S. M.·Leung, N. H.·Cobey, S.·Cowling, B. J.·Bedford, T.·Hensley, S. E.·Bloom, J. D.

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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 towards 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 versus 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 versus recombinant protein vaccines can elicit different relative titer boosts against different subsets of viral strains, a phenomenon that could impact vaccine effectiveness. ImportanceInfluenza 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.

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Loes, A. N., Tarabi, R. A., Li, S. H., Atkinson, R. K., Huddleston, J., Kikawa, C., Griffths, T., Drapeau, E. M., Wong, S.-S., Cheng, S. M., Leung, N. H., Cobey, S., Cowling, B. J., Bedford, T., Hensley, S. E., Bloom, J. D.. 2026-02-23. Strain-specific differences in the response to egg-derived versus recombinant protein influenza vaccines. https://doi.org/10.64898/2026.02.23.707528

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