Immunogenicity of High-Dose Egg-Based, Recombinant, and Cell Culture-Based Influenza Vaccines Compared With Standard-Dose Egg-Based Influenza Vaccine Among Health Care Personnel Aged 18-65 Years in 2019-2020.

Allison L Naleway ,F Liaini Gross ,Brendan Flannery ,Sarah Spencer ,Shivaprakash Gangappa ,Tnelda Zunie ,Min Z Levine ,Zuha Jeddy ,Suryaprakash Sambhara ,Sara S Kim ,Kempapura Murthy ,Weiping Cao ,Margarita Mishina ,Manjusha Gaglani ,Alicia M Fry ,Mark G Thompson ,Holly Groom ,Meredith G Wesley ,Lauren Grant ,Danielle Hunt ,Sarah Ball ,Laura J Edwards ,Fatimah S Dawood

doi:10.1093/ofid/ofad223

Abstract

Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020). In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4. Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes. HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.

Full Text