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

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. Clinical Trials Registration. NCT05514002.