Comparison of A(H3N2) neutralizing antibody responses elicited by 2018–2019 season quadrivalent influenza vaccines derived from eggs, cells, and recombinant hemagglutinin

Wei Wang, Esmeralda Alvarado-Facundo, Russell Vassell, Limone Collins, Rhonda E. Colombo, Anuradha Ganesan, Casey Geaney, David Hrncir, Tahaniyat Lalani, Ana Elizabeth Markelz, Ryan C. Maves, Bruce McClenathan, Katrin Mende, Stephanie A. Richard, Christina Schofield, Srihari Seshadri, Christina Spooner, Gregory C. Utz, Tyler E. Warkentien, Min LevineChristian L. Coles, Timothy H. Burgess, Maryna Eichelberger, Carol D. Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background. Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. Methods. Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018–2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. Results. All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019–2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. Conclusion. Egg- and cell-derived 2018–2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.

Original languageEnglish
Pages (from-to)E4312-E4320
JournalClinical Infectious Diseases
Issue number11
StatePublished - 1 Dec 2021
Externally publishedYes


  • Egg-adaptive mutations
  • Hemagglutinin
  • Influenza vaccine
  • Neutralizing antibodies
  • Vaccine effectiveness


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