Andrea N. Loes, Rosario Araceli L Tarabi, Shuk Hang Li, Reilly K. Atkinson, John Huddleston, Caroline Kikawa, Tachianna Griffiths, Elizabeth M. Drapeau, Sook‐San Wong, SW Cheng, Nancy H. L. Leung, S. Cobey, Benjamin J. Cowling, Trevor Bedford, Scott E. Hensley, Jesse D. Bloom
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.