Cell-Mediated and Humoral Immune Responses to COVID-19 Following Co-Administration of COVID-19 and Influenza Vaccines in Healthy Volunteers

Background: The immunogenicity of co-administering coronavirus disease (COVID-19) and influenza vaccines is not well-established, especially regarding cell-mediated immune response (CMIR). We aimed to evaluate both CMIR and humoral immune response (HIR) in this context. Materials and Methods: In this pilot randomized controlled trial, 36 healthy adults were randomly assigned (1:1:1) to receive the influenza vaccine, the COVID-19 vaccine, or co-administration. CMIR was assessed using the interferon-gamma enzyme-linked immunospot assay, and HIR was measured by anti-receptor-binding domain immunoglobulin G against severe acute respiratory syndrome coronavirus 2, both before and 4 weeks after vaccination. The primary outcome was the geometric mean ratio (GMR) of post-vaccination responses, with a lower bound of the 95% confidence interval (CI) >0.67 as the noninferiority margin. Results: GMRs between co-administration and COVID-19 vaccine were 1.03 (95% CI: 0.43-2.44) for CMIR and 0.82 (95% CI: 0.52-1.29) for HIR; both failed to meet the noninferiority margin. The immune response magnitude was 1.60 (95% CI: 0.64-4.00) for CMIR and 0.80 (95% CI: 0.41-1.58) for HIR. Conclusions: Post-vaccination immune responses were overall comparable, although the confidence intervals fell below the statistical noninferiority threshold. In terms of response magnitude, CMIR increased more and HIR increased less in the co-administration group. These findings may support a co-administration strategy, but larger trials are needed for confirmation.