Exploratory evidence of mitigated immune imprinting following concomitant COVID-19 and influenza vaccination

Concomitant administration of coronavirus disease (COVID-19) and influenza vaccination schedules has been widely adopted. However, long-term data on the immunological impact, particularly on variant-specific responses, remain limited. In this 10-month prospective study, 80 participants (40 per group) received either a concomitant bivalent COVID-19 mRNA booster and quadrivalent influenza vaccination (Group C) or separate vaccinations (Group S) at least 4 weeks apart. Immunogenicity was evaluated using an anti-S IgG electrochemiluminescence immunoassay, anti- receptor-binding domain (RBD) IgG enzyme-linked immunosorbent assay, focus reduction neutralisation test (FRNT), and hemagglutination-inhibition assay. Both Groups C and S elicited robust immune responses for up to 10 months with no immune interference, as antibody responses against wild-type (WT) and Omicron BA.5 remained comparable between the groups. Notably, neutralising antibody titre against Omicron BA.5 were higher in Group C at 1 month post-vaccination, with significantly higher neutralising potency (FRNT₅₀/anti-RBD IgG titer ratio) against Omicron BA.5 and a higher BA.5-to-WT ratio in FRNT. These findings may suggest alleviated immune imprinting, although this remains exploratory and requires further validation. For influenza, the overall antibody responses were comparable between the two groups. These findings support the feasibility of concomitant influenza and COVID-19 vaccination, without evidence of immune interference. Moreover, the enhanced variant-specific immune responses with concomitant administration suggest a potential immunological benefit, warranting future investigation.