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Randomized Controlled Trial
. 2023 Feb 8;76(3):e1168-e1176.
doi: 10.1093/cid/ciac683.

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

Manjusha Gaglani  1   2 , Sara S Kim  3 , Allison L Naleway  4 , Min Z Levine  3 , Laura Edwards  5 , Kempapura Murthy  1 , Kayan Dunnigan  1 , Tnelda Zunie  1 , Holly Groom  4 , Sarah Ball  5 , Zuha Jeddy  5 , Danielle Hunt  5 , Meredith G Wesley  5 , Suryaprakash Sambhara  3 , Shivaprakash Gangappa  3 , Lauren Grant  3 , Weiping Cao  3 , F Liaini Gross  3 , Margarita Mishina  3 , Alicia M Fry  3 , Mark G Thompson  3 , Fatimah S Dawood  3 , Brendan Flannery  3
Affiliations
Randomized Controlled Trial

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

Manjusha Gaglani et al. Clin Infect Dis. .

Abstract

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.

Keywords: Flublok Quadrivalent; Flucelvax Quadrivalent; healthcare personnel; immunogenicity; influenza vaccines.

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Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Consolidated Standards of Reporting Trials diagram for participants re-enrolled in the second study year (2019–2020 influenza season). Abbreviations: ccIIV, cell culture–based inactivated influenza vaccine (Flucelvax Quadrivalent); IIV, inactivated influenza vaccine (Fluzone Quadrivalent); RIV, recombinant-hemagglutinin influenza vaccine (Flublok Quadrivalent); S2, post-vaccination blood (21–62 days after); year 1, 2018–2019; year 2, 2019–2020.
Figure 2.
Figure 2.
Forest plot of geometric mean hemagglutination inhibition (HI) antibody titer ratios (geometric mean titer [GMT] ratios) at 1 month post-vaccination by 2-season vaccine combination. Figure shows ratios comparing year 2 post-vaccination HI antibody titers in each non–egg-based 2-season vaccine combination group to HI titers among participants who received standard-dose egg-based inactivated influenza vaccine both seasons (IIV/IIV; referent group). HI antibody titers were measured against cell-propagated antigens of 2019–2020 vaccine reference strains A/Idaho/07/2018 (H1N1)pdm09 (A/Brisbane/02/2018-like), A/Kansas/14/2017 (H3N2), B/Colorado/06/2017(Victoria), and B/Phuket/3073/2013(Yamagata). The forest plot depicts GMT ratios for each year 1/year 2 vaccine combination, calculated using log-transformed GMTs. Horizontal lines represent the 99.3% CI, and solid circles represent the point estimates. All estimates to the right of the null value of 1 favor the corresponding year 1/year 2 vaccine combination over the IIV/IIV referent group. *Applying a Bonferroni correction for multiple comparisons, P <.007 for GMT ratio is statistically significant. Abbreviations: ccIIV, cell culture–based inactivated influenza vaccine (Flucelvax Quadrivalent); CI, confidence interval; IIV, inactivated influenza vaccine (Fluzone Quadrivalent); RIV, recombinant-hemagglutinin influenza vaccine (Flublok Quadrivalent).
Figure 3.
Figure 3.
Forest plot of MFR in geometric mean hemagglutination inhibition (HI) antibody titer (geometric mean titer [GMT]) at 1 month post-vaccination by 2-season vaccination combination. MFR and 99.3% CIs were defined as the geometric mean of the ratio of post-vaccination titer and pre-vaccination titer for each participant. *Applying a Bonferroni correction for multiple comparisons, P <.007 for GMT ratio is statistically significant. Abbreviations: ccIIV, cell culture–based inactivated influenza vaccine (Flucelvax Quadrivalent); CI, confidence interval; MFR, mean fold-rise; IIV, inactivated influenza vaccine (Fluzone Quadrivalent); RIV, recombinant-hemagglutinin influenza vaccine (Flublok Quadrivalent).
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