Co-administration of seasonal quadrivalent influenza and COVID-19 vaccines leads to enhanced immune responses to influenza virus and reduced immune responses to SARS-CoV-2 in naive mice.

The ongoing co-circulation of influenza viruses and severe acute respiratory disease coronavirus 2 (SARS-CoV-2) presents significant public health challenges. Vaccination is a pivotal tool to tackle infections and severe disease. Administering both the influenza and coronavirus disease 2019 (COVID-19) vaccines simultaneously could simplify vaccine delivery and is already practice in several countries. In this study, we assessed the protective efficacy and humoral immune responses elicited by concomitant administration of a quadrivalent influenza vaccine (QIV) and the Pfizer-BioNTech mRNA COVID-19 vaccine (BNT162b2) in naïve BALB/c mice. We included three ways of co-administration: a) both vaccines at contralateral limbs, b) both vaccines at ipsilateral limbs and c) admixture of the two vaccines before administration. The last regimen was included since it has been shown that the lipid nanoparticles used for mRNA vaccines can also have an adjuvant effect on protein-based antigens. Notably, co-administration of QIV and COVID-19 mRNA vaccine led to significantly higher hemagglutinin inhibiting (HAI) and binding antibody titers compared to QIV only vaccination, especially in the ipsilateral and admixed groups. Conversely, ipsilateral administration and administration of an admixed vaccine had a slightly negative impact on SARS-CoV-2 binding and neutralization titers. These findings support the hypothesis that the co-administration of QIV and COVID-19 mRNA vaccines can induce robust antibody responses, which are indicative of protective immune responses against both infectious agents.