Long-Term Durability and Dynamics of Anti-S-RBD IgG Response in Healthcare Workers: A Comparative Analysis of Homologous and Heterologous SARS-CoV-2 Vaccination Schedules in a 1-Year Serial Cross-Sectional Study.

BACKGROUND The waning of post-vaccination immunity necessitates effective booster strategies, especially for high-risk healthcare workers (HCWs). This study aimed to compare the 1-year antibody response dynamics of homologous and heterologous SARS-CoV-2 vaccination schedules in Turkish HCWs. MATERIAL AND METHODS This prospective, serial cross-sectional study included 307 HCWs grouped by vaccination history reflecting the national vaccination program: homologous inactivated (SSS, 3 doses of CoronaVac), homologous mRNA (BBB, 3 doses of mRNA-BNT162b2), and heterologous mRNA-boosted (SSB, SSBB, SSBBB; where S represents CoronaVac and B represents BNT162b2). Anti-S-RBD IgG levels were measured at 3 time points between December 2021 and September 2022. Statistical analyses were performed using Mann-Whitney U and Kruskal-Wallis tests. RESULTS The SSS group showed significantly lower antibody levels (median: 77.5 AU/mL) compared to all mRNA-containing groups (P<0.001). No significant difference was found between the BBB group and heterologous regimens (P>0.05), indicating an mRNA booster dose achieves a humoral response comparable to a full mRNA series. Antibody levels waned significantly over time in all mRNA-containing groups (P<0.05) but remained stable in the SSS group (P=0.987). Natural infection significantly increased antibody levels only in the SSS group (P=0.014), suggesting a ceiling effect in mRNA-vaccinated individuals. No serious adverse events were reported. CONCLUSIONS Homologous inactivated vaccination results in lower but more stable antibody levels. In contrast, both homologous mRNA and heterologous mRNA-boosted schedules achieve higher, albeit waning, antibody titers. The presence of at least 1 mRNA vaccine dose is the primary driver of high anti-S-RBD IgG levels. These findings support using heterologous mRNA boosters to enhance humoral immunity in individuals primed with inactivated vaccines.