Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18–64 Years: A Randomized Open-Label Trial
Fatimah S. Dawood, Allison L. Naleway, Brendan Flannery, Min Z. Levine, Kempapura Murthy, Suryaprakash Sambhara, Shivaprakash Gangappa, Laura Edwards, Sarah W. Ball, Lauren Grant, Edward A. Belongia, Kelsey Bounds, Weiping Cao, F. Liaini Gross, Holly C. Groom, Alicia M. Fry, Danielle Rentz Hunt, Zuha Jeddy, Margarita Mishina, Sara Kim, Meredith G. Wesley, Sarah Spencer, Mark G. Thompson, Manjusha Gaglani
Abstract
BACKGROUND: RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. METHODS: During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. RESULTS: In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2-1.9) for A/H1N1, 3.0 (95% CI: 2.4-3.7) for A/H3N2, 1.1 (95% CI: .9-1.4) for B/Yamagata, and 1.1 (95% CI: .9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. CONCLUSIONS: RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4. CLINICAL TRIALS REGISTRATION: NCT03722589.