Effect of Repeat Vaccination on Immunogenicity of Quadrivalent Cell-Culture and Recombinant Influenza Vaccines Among Healthcare Personnel Aged 18-64 Years: A Randomized, Open-Label Trial.

Background: Antibody responses to non-egg-based standard-dose cell-culture influenza vaccine (containing 15 µg hemagglutinin [HA]/component) and recombinant vaccine (containing 45 µg HA/component) during consecutive seasons have not been studied in the United States.
Methods: In a randomized trial of immunogenicity of quadrivalent influenza vaccines among healthcare personnel (HCP) aged 18-64 years over 2 consecutive seasons, HCP who received recombinant-HA influenza vaccine (RIV) or cell culture-based inactivated influenza vaccine (ccIIV) during the first season (year 1) were re-randomized the second season of 2019-2020 (year 2 [Y2]) to receive ccIIV or RIV, resulting in 4 ccIIV/RIV combinations. In Y2, hemagglutination inhibition antibody titers against reference cell-grown vaccine viruses were compared in each ccIIV/RIV group with titers among HCP randomized both seasons to receive egg-based, standard-dose inactivated influenza vaccine (IIV) using geometric mean titer (GMT) ratios of Y2 post-vaccination titers.
Results: Y2 data from 414 HCP were analyzed per protocol. Compared with 60 IIV/IIV recipients, 74 RIV/RIV and 106 ccIIV/RIV recipients showed significantly elevated GMT ratios (Bonferroni corrected P < .007) against all components except A(H3N2). Post-vaccination GMT ratios for ccIIV/ccIIV and RIV/ccIIV were not significantly elevated compared with IIV/IIV except for RIV/ccIIV against A(H1N1)pdm09.
Conclusions: In adult HCP, receipt of RIV in 2 consecutive seasons or the second season was more immunogenic than consecutive egg-based IIV for 3 of the 4 components of quadrivalent vaccine. Immunogenicity of ccIIV/ccIIV was similar to that of IIV/IIV. Differences in HA antigen content may play a role in immunogenicity of influenza vaccination in consecutive seasons.
Clinical Trials Registration: NCT03722589.
Competing Interests: Potential conflicts of interest. M. G. reports grants from the unrelated CDC (US Ambulatory Flu/COVID Vaccine Effectiveness Network, Hospitalized Adult Influenza Vaccine Effectiveness Network [HAIVEN], Refining Effectiveness Estimates of Influenza Vaccines Synergizing Epidemiolgy and Incidence Methods for Influenza and Other Acute Respiratory Viral Illness [SYNERGY] Studies), unrelated CDC-Abt Associates (Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel [RECOVER] and Pediatric Research Observing Trends and Exposures in COVID-19 Timelines [PROTECT] cohort studies), unrelated CDC–Vanderbilt University Medical Center (Influenza and Other Viruses in the Acutely Ill [IVY] Study), unrelated CDC-Westat (Virtual Network: Investigating the Risk of COVID-19-Associated Outcomes and COVID-19 Vaccine Effectiveness Using Integrated Medical and Public Health Records [VISION-COVID] Study), unrelated Janssen (RSV Severity Birth Cohort Study), and unrelated Pfizer (Education for Men B Vaccine in Adolescents); being the co-chair of the Texas Pediatric Society's (Texas Chapter of the American Academy of Pediatrics) Infectious Diseases and Immunization Committee (2016–2022). A. L. N. reports funding from Pfizer and Vir Biotechnology for unrelated studies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)