Antibody response after two doses of homologous or heterologous SARS‐CoV‐2 vaccines in healthcare workers at health promotion centers: A prospective observational study

Assaying of anti‐spike‐protein receptor‐binding domain (S‐RBD) antibodies are used to aid evaluations of the immune statuses of individuals. The aim of this study was to determine the antibody response after two doses of homologous or heterologous severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines and to identify the factors affecting this response among healthcare workers (HCWs) at health promotion centers. In this prospective observational study, 1095 consenting HCWs were recruited from 16 health checkup centers and were tested at T0 (day of first dose), T1‐1 (1 month after first dose), T2‐0 (day of second dose), T2‐1 (1 month after second dose), and T2‐3 (3 months after second dose). SARS‐CoV‐2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS‐CoV‐2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). At T1‐1, anti‐SARS‐CoV‐2 S‐RBD IgG levels were significantly higher in participants who received messenger RNA (mRNA) vaccines than in those who received viral vector vaccines (p < 0.001). At T2‐1, anti‐SARS‐CoV‐2 S‐RBD IgG levels were about 10 times higher than at T1‐1 in participants who received homologous mRNA vaccines, which decreased to a third of those at T2‐3. Anti‐SARS‐CoV‐2 S‐RBD IgG levels were highest among those who received homologous mRNA vaccines, followed by heterologous mRNA viral vector vaccines and homologous viral vector vaccines at T2‐3 (p < 0.001). In a multivariable linear regression analysis, being female, taking at least one mRNA vaccine, and having a history of recovery from coronavirus disease 2019 (COVID‐19) were significantly associated with anti‐S‐RBD levels. Anti‐SARS‐CoV‐2 S‐RBD IgG levels were decreased at 3 months after two‐dose vaccinations and were associated with sex, vaccine type, and COVID‐19 history.