Immunogenicity and safety of concomitant bivalent COVID-19 and quadrivalent influenza vaccination: Implications of immune imprinting and interference

OBJECTIVES:Concomitant COVID-19 and influenza vaccination would be an efficient strategy. While the co-administration of monovalent COVID-19 and influenza vaccinations showed acceptable immunogenicity, it remains unknown whether the bivalent COVID-19 vaccine could intensify immune interference. We aimed to evaluate the immunogenicity and safety of concomitant BA.5-based bivalent COVID-19 and influenza vaccination. METHODS:An open-label, non-randomized clinical trial was conducted for 154 age- and sex-matched healthy adults between October and December 2022. Participants received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (group C) or separate vaccinations (group S) at least four weeks apart. Solicited and unsolicited adverse events were reported up to 6 months post-vaccination. Immunogenicity was evaluated by anti-S IgG electrochemiluminescence immunoassay, focus reduction neutralization test and hemagglutination inhibition assay. RESULTS:Group C did not meet the non-inferiority criteria for the seroconversion rates of anti-S IgG and neutralizing antibodies against the wild-type SARS-CoV-2 strain compared to group S (44.2% versus 46.8%, difference of -2.6% [95% CI -18 to 13.4]; 44.2% versus 57.1%, difference of -13.0% [95% CI -28.9 to 2.9]). However, group C showed a stronger post-vaccination neutralizing antibody response against Omicron BA.5 (72.7% versus 64.9%). Post-vaccination geometric mean titers for SARS-CoV-2 and influenza strains were similar between groups, except for influenza B/Victoria. Most adverse events were mild and comparable between the study groups. CONCLUSIONS:Concomitant administration of bivalent COVID-19 mRNA and quadrivalent influenza vaccines showed tolerable safety profiles and sufficient immunogenicity, particularly attenuating immune imprinting induced by prior ancestral vaccine strains.