Immunogenicity and Safety of the COVID-19 mRNA Vaccine Coadministered with Influenza and 23-valent Pneumococcal Polysaccharide Vaccines

Co-administering vaccines can effectively enhance vaccination uptake in adults. Despite the potential benefits, there is limited data supporting this practice. We investigated the immunogenicity and safety of co-administering COVID-19 mRNA, Influenza, and Pneumococcal (PPSV23) vaccines in adults. As part of the national vaccination program, 3,104 adults received a fourth dose (2nd booster) of an mRNA COVID-19 vaccine alone or coadministered with an influenza vaccine, with or without PPSV23 from January to December 2022. We measured SARS-CoV-2 anti-spike and anti-receptor binding domain (RBD) IgG concentrations and neutralization activity before and one month after vaccination. We estimated the odds of a ≥2-fold geometric mean fold rise (GMFR) and adverse events (AEs) using logistic regression models. The median age of the 3,104 participants was 70 years (IQR: 60-77); 1,670 (54%) were female. Anti-spike IgG GMFRs were 1.95, 1.56, and 1.42, while for neutralization activity, values were 8.99, 12.42, and 8.23, in the COVID-19, COVID-19+Influenza, and COVID-19+Influenza+PPSV23 groups, respectively. The adjusted odds of a ≥2-fold anti-spike IgG GMFR were 0.64 (p < 0.001) and 0.43 (p < 0.001), and for neutralization activity, 0.96 (p = 0.833) and 0.97 (p = 0.954), for COVID-19+Influenza and COVID-19+Influenza+PPSV23, respectively. The odds for anti-RBD GMFRs followed similar patterns. Systemic AEs were more common in the COVID-19+Influenza+PPSV23 group (adjusted OR: 2.04, p < 0.001), though no serious AEs were reported. Co-administering COVID-19, Influenza, and PPSV23 vaccines seems feasible, without significantly impairing neutralizing antibody responses. These findings support the recommendation for vaccine coadministration in adults.