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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 1 2 , Rosario Araceli L Tarabi 2 , Shuk Hang Li 3 , Reilly K Atkinson 3 , John Huddleston 4 , Caroline Kikawa 2 5 6 , Tachianna Griffiths 3 , Elizabeth M Drapeau 3 , Sook-San Wong 7 , Samuel M S Cheng 7 , Nancy H L Leung 7 , Sarah Cobey 8 , Benjamin J Cowling 7 , Trevor Bedford 1 4 , Scott E Hensley 3 , Jesse D Bloom 1 2
Affiliations
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.
. 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 1 2 , Rosario Araceli L Tarabi 2 , Shuk Hang Li 3 , Reilly K Atkinson 3 , John Huddleston 4 , Caroline Kikawa 2 5 6 , Tachianna Griffiths 3 , Elizabeth M Drapeau 3 , Sook-San Wong 7 , Samuel M S Cheng 7 , Nancy H L Leung 7 , Sarah Cobey 8 , Benjamin J Cowling 7 , Trevor Bedford 1 4 , Scott E Hensley 3 , Jesse D Bloom 1 2
Affiliations
- PMID: 42200639
- DOI: 10.1128/jvi.00317-26
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.