Influenza A(H3N2) Antibody Responses to Standard-Dose Versus Enhanced Influenza Vaccine Immunogenicity in Older Adults and Prior Season's Vaccine Status

J Infect Dis. 2024 May 15;229(5):1451-1459. doi: 10.1093/infdis/jiad497.


Background: Annual influenza vaccination is recommended for older adults but repeated vaccination with standard-dose influenza vaccine has been linked to reduced immunogenicity and effectiveness, especially against A(H3N2) viruses.

Methods: Community-dwelling Hong Kong adults aged 65-82 years were randomly allocated to receive 2017-2018 standard-dose quadrivalent, MF59-adjuvanted trivalent, high-dose trivalent, and recombinant-HA quadrivalent vaccination. Antibody response to unchanged A(H3N2) vaccine antigen was compared among participants with and without self-reported prior year (2016-2017) standard-dose vaccination.

Results: Mean fold rise (MFR) in antibody titers from day 0 to day 30 by hemagglutination inhibition and virus microneutralization assays were lower among 2017-2018 standard-dose and enhanced vaccine recipients with (range, 1.7-3.0) versus without (range, 4.3-14.3) prior 2016-2017 vaccination. MFR was significantly reduced by about one-half to four-fifths for previously vaccinated recipients of standard-dose and all 3 enhanced vaccines (β range, .21-.48). Among prior-year vaccinated older adults, enhanced vaccines induced higher 1.43 to 2.39-fold geometric mean titers and 1.28 to 1.74-fold MFR versus standard-dose vaccine by microneutralization assay.

Conclusions: In the context of unchanged A(H3N2) vaccine strain, prior-year vaccination was associated with reduced antibody response among both standard-dose and enhanced influenza vaccine recipients. Enhanced vaccines improved antibody response among older adults with prior-year standard-dose vaccination.

Keywords: antibody response; influenza vaccine; older adults; repeated vaccination.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Viral* / blood
  • Antibody Formation / immunology
  • Female
  • Hemagglutination Inhibition Tests*
  • Hong Kong / epidemiology
  • Humans
  • Immunogenicity, Vaccine
  • Influenza A Virus, H3N2 Subtype* / immunology
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / immunology
  • Influenza, Human* / immunology
  • Influenza, Human* / prevention & control
  • Male
  • Squalene / administration & dosage
  • Squalene / immunology
  • Vaccination / methods