Comparison of Human H3N2 Antibody Responses Elicited by Egg-Based, Cell-Based, and Recombinant Protein-Based Influenza Vaccines During the 2017-2018 Season

Abstract

Background: The H3N2 component of egg-based 2017-2018 influenza vaccines possessed an adaptive substitution that alters antigenicity. Several influenza vaccines include antigens that are produced through alternative systems, but a systematic comparison of different vaccines used during the 2017-2018 season has not been completed.

Methods: We compared antibody responses in humans vaccinated with Fluzone (egg-based, n = 23), Fluzone High-Dose (egg-based, n = 16), Flublok (recombinant protein-based, n = 23), or Flucelvax (cell-based, n = 23) during the 2017-2018 season. We completed neutralization assays using an egg-adapted H3N2 virus, a cell-based H3N2 virus, wild-type 3c2.A and 3c2.A2 H3N2 viruses, and the H1N1 vaccine strain. We also performed enzyme-linked immunosorbent assays using a recombinant wild-type 3c2.A hemagglutinin. Antibody responses were compared in adjusted analysis.

Results: Postvaccination neutralizing antibody titers to 3c2.A and 3c2.A2 were higher in Flublok recipients compared with Flucelvax or Fluzone recipients (P < .01). Postvaccination titers to 3c2.A and 3c2.A2 were similar in Flublok and Fluzone High-Dose recipients, though seroconversion rates trended higher in Flublok recipients. Postvaccination titers in Flucelvax recipients were low to all H3N2 viruses tested, including the cell-based H3N2 strain. Postvaccination neutralizing antibody titers to H1N1 were similar among the different vaccine groups.

Conclusions: These data suggest that influenza vaccine antigen match and dose are both important for eliciting optimal H3N2 antibody responses in humans. Future studies should be designed to determine if our findings directly impact vaccine effectiveness.

Clinical trials registration: NCT03068949.

Keywords: antibodies; hemagglutinin; influenza; vaccine.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Pre- and postvaccination titers in sera from individuals vaccinated with Flublok, Flucelvax, Fluzone, or Fluzone HD during the 2017–2018 season. Thick horizontal lines show the geometric mean titers and 95% confidence intervals. Significant P values (<.05) for postvaccination titers adjusted for prevaccination titers, year of birth, and vaccination history and adjusted for multiple comparisons are indicated above each graph. A, Neutralizing antibody titers (foci reduction neutralization test [FRNT]90) to wild-type 3c2.A virus. B, Neutralizing antibody titers (FRNT90) to wild-type 3c2.A2 virus. C, Hemagglutinin ELISA IgG concentrations to wild-type 3c2.A virus (mg/mL). D, Neutralizing antibody titers (FRNT90) to 3c2.A/egg virus. E, Neutralizing antibody titers (FRNT90) to 3c2.A/cell virus. F, Neutralizing antibody titers (FRNT90) to H1N1 virus. Abbreviations: ELISA, enzyme-linked immunosorbent assay; HD, high-dose; Ig, immunoglobulin.

Figure 2.

Heat map of fold change in geometric mean neutralizing antibody levels (foci reduction neutralization test90) and ELISA titers (immunoglobulin G concentration) upon influenza vaccination during the 2017–2018 season. Postvaccination titers were divided by prevaccination titers to calculate fold change. Darker colors indicate higher fold changes. Abbreviations: ELISA, enzyme-linked immunosorbent assay; HD, high-dose.