Replication Data for: Impact of Repeated Variant Exposures on Cellular and Humoral Immunogenicity induced by SARS-CoV-2 Vaccines

Background/Objectives: The emergence of omicron variant has complicated COVID-19 control and prompted vaccine updates. Recent studies show that a fourth dose significantly protects against infection and severe disease, though long-term immunity data remains limited. This study aimed to assess Anti-S-RBD antibodies and interferon-γ levels in healthcare workers 12 months after a fourth SARS-CoV-2 vaccine. Methods: In this prospective cohort study, 549 healthcare workers were categorized by initial vaccination schedule, with 229 individuals receiving the fourth SARS-CoV-2 vaccine dose. Blood samples were collected from all participants 12 months post-vaccination. Results: Significant differences in Anti-S-RBD antibody levels were observed between those receiving a fourth dose and those who did not, while no differences were seen in interferon-γ levels. Regarding primary vaccine schedules, participants vaccinated with ChAdOx1 (single or double dose) had notably lower antibody levels compared to those who received mRNA-based vaccines. Additionally, the study shows higher frequency of multiple infections among those with a single-dose ChAdOx1 primary schedule (OR: 6.24; 95% CI: 1.25–31.15; p<0.01). After 12 months, there were no significant differences in humoral and cellular immunity response between volunteers primoinfected or reinfected across different periods by omicron variant. A multivariable analysis revealed an association between high antibody levels (>6000 U/mL) and interferon-γ levels (OR: 3.13; 95% CI: 1.3–7.7; p<0.05). Conclusions: Overall, mRNA-based vaccines exhibited stronger long-term immunogenicity. Repeated exposure to the omicron variant reduces immune imprinting from the wild-type SARS-CoV-2. An association was observed between high antibody levels and a strong cellular response, although this was not linear