Longitudinal Comparison of Three T-Cell Assays and Three Antibody Assays Against SARS-CoV-2 Following Homologous mRNA-1273/mRNA-1273/mRNA-1273 and Heterologous ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naïve Healthcare Workers

<b>Background</b>: Cellular and humoral immunity are key to the immune response against SARS-CoV-2, but the comparability and correlation across different assays remain underexplored. This study compares three T-cell and three antibody assays in two vaccine groups. <b>Methods</b>: This prospective longitudinal cohort study involved 46 naïve healthcare workers: a total of 11 in the homologous mRNA-1273 group (three doses) and 35 in the heterologous ChAd group (two ChAd doses followed by a BNT booster). Blood samples were collected at five time points. Cellular immunity was assessed using ELISPOT and two commercial interferon-gamma release assays: (IGRA)-QuantiFERON SARS-CoV-2 (QF) and Covi-FERON ELISA (CoVF). Humoral immunity was evaluated using total and IgG antibody assays and a surrogate virus neutralization test. <b>Results</b>: The mRNA-1273 group exhibited stronger and more consistent responses than the ChAd group. The correlations between ELISPOT and IGRA varied from weak to moderate (ρ = 0.300-0.410), while QF-IGRA and CoVF-IGRA showed stronger correlations (ρ = 0.700-0.737). The ELISPOT assay showed substantial agreement with QF [Ag2]-IGRA (k = 0.697-0.774) and CoVF [O-sp]-IGRA (k = 0.641-0.718), and an 80.4% agreement rate (k = 0.608) was found between the QF [Ag2]- and CoVF [O-sp]-IGRA tests. Three antibody assays demonstrated very strong correlations with each other and substantial to near-perfect agreement with ELISPOT (k = 0.866-0.949), QF [Ag2]-IGRA (k = 0.807-0.831), and CoVF [O-sp]-IGRA (k = 0.753-0.777). <b>Conclusions</b>: SARS-CoV-2-specific cellular and antibody responses vary by platform and vaccine type, highlighting the importance of measuring both T-cell and B-cell responses using multiple assays to comprehensively assess immune status.