Relative Effectiveness and Immunogenicity of Quadrivalent Recombinant Influenza Vaccine Versus Egg-Based Inactivated Influenza Vaccine Among Adults Aged 18-64 Years: Results and Experience From a Randomized, Double-Blind Trial.

Authors

Lauren Grant
Jennifer A Whitaker
Sarang K Yoon
Karen Lutrick
Shivam Bhargava
C Perry Brown
Emily Zaragoza
Rebecca V Fink
Jennifer Meece
Kristina Wielgosz
Hana El Sahly
Kurt T Hegmann
Ashley A Lowe
Alia Southworth
Tanya Tatum
Sarah W Ball
Min Z Levine
Matthew S Thiese
Steph Battan-Wraith
John Barnes
Andrew L Phillips
Alicia M Fry
Fatimah S Dawood
Randomized Assessment of Influenza Vaccine Efficacy Network (RAIVEN)

Publication Date

10-1-2024

Journal

Open Forum Infectious Diseases

DOI

10.1093/ofid/ofae559

PMID

39416990

PMCID

PMC11482004

PubMedCentral® Posted Date

9-26-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

immunogenicity, influenza, influenza vaccines, relative effectiveness, clinical trial

Abstract

BACKGROUND: Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza vaccines (SD IIV). This randomized trial evaluated the relative vaccine effectiveness (VE) and immunogenicity of RIV versus SD IIV in frontline workers and students aged 18-64 years.

METHODS: Participants were randomized to receive RIV or SD IIV and followed for reverse-transcription polymerase chain reaction (RT-PCR)-confirmed influenza during the 2022-2023 influenza season. Sera were collected from a subset of participants before and at 1 and 6 months postvaccination and tested by hemagglutination inhibition for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria and against cell-grown vaccine reference viruses for A/H1N1 and A/H3N2.

RESULTS: Overall, 3988 participants were enrolled and vaccinated (25% of the trial sample size goal); RT-PCR-confirmed influenza occurred in 20 of 1963 RIV recipients and 28 of 1964 SD IIV recipients. Relative VE was 29% (95% confidence interval [CI], -26% to 60%). In the immunogenicity substudy (n = 118), the geometric mean titer ratio (GMTR) comparing RIV to SD IIV at 1 month was 2.3 (95% CI, 1.4-3.7) for cell-grown A/H1N1, 2.1 (95% CI, 1.3-3.4) for cell-grown A/H3N2, 1.1 (95% CI, .7-1.6) for B/Victoria, and 1.4 (95% CI, .9-2.0) for B/Yamagata. At 6 months, GMTRs were >1 against A/H1N1, A/H3N2, and B/Yamagata.

CONCLUSIONS: Relative VE of RIV compared to SD IIV did not reach statistical significance, but RIV elicited more robust humoral immune responses to 2 of 4 vaccine viruses at 1 month and 3 of 4 viruses at 6 months after vaccination, suggesting possible improved and sustained immune protection from RIV.

Comments

Clinical Trials Registration. NCT05514002.