Factors impacting antibody kinetics, including fever and vaccination intervals, in SARS-CoV-2-naïve adults receiving the first four mRNA COVID-19 vaccine doses.

To evaluate the antibody response following the initial four doses of mRNA vaccines (BNT162b2 or mRNA-1273) in SARS-CoV-2-naïve healthy adults and investigate factors influencing antibody titer increases, this prospective cohort study was conducted in Japan from March 2021. The study included participants who received either the 1st and 2nd doses (n = 467), 3rd dose (n = 157), or 4th dose (n = 89). Blood samples were collected before and up to 6 months after each dose, and anti-receptor-binding domain antibody levels were measured. Multivariate analysis (usin multiple linear regression or linear mixed models) revealed several factors significantly associated with higher post-vaccination antibody levels, including mRNA-1273 vaccine (after the 1st and 2nd dose), male gender (after the 3rd and 4th doses), younger age (after the 1st and 2nd dose), non-smoking status (after the 2nd dose), non-use of immunosuppressive agents (after the 1st dose), higher pre-vaccination antibody titers (after the 2nd, 3rd, and 4th doses), and higher post-vaccination fever (after the 2nd and 4th doses). Furthermore, longer intervals since the last dose were significantly associated with higher antibody levels after the 3rd and 4th doses. These findings provide valuable insights for optimizing vaccination strategies.

Antibody responses after BNT162b2 vaccination in Japanese geriatric intermediate care facilities.

Background: To evaluate antibody responses against the primary series of vaccination of severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2] vaccines in the staff and residents of Japanese geriatric intermediate care facilities. Methods: All subjects (159 staff and 96 residents) received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Baseline data of subject were collected using a structured form. Serum samples were collected three times: before vaccination, 3 weeks after the first dose, and 4 weeks after the second dose, and anti-receptor binding domain of the spike protein of SARS-CoV-2 [anti-RBD] IgG was measured using two immunoassays. Results: After the second dose, geometric mean titers [GMT] of anti-RBD with both the Abbott and Roche assay were significantly lower in residents than staff (2282 AU/mL vs. 8505 AU/mL, and 258 U/mL vs. 948 U/mL, respectively). Multivariate analysis of characteristics affecting antibody responses (≥1280 AU/mL for Abbott and > 210 U/mL for Roche) showed lower odds ratios [ORs] for older age (adjusted OR per 10 year increase [aOR] = 0.62, 95 % confidence interval [95 %CI]; 0.38-1.02), steroid usage (aOR = 0.09, 95 %CI; 0.01-0.60) and regular nonsteroidal anti-inflammatory drugs [NSAIDs] usage (aOR = 0.16, 95 %CI; 0.03-0.88). Conclusions: Elderly people and steroid and NSAID users had lower antibody responses following the second vaccine dose.

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan.

BACKGROUND: Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays. METHODS: This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays. RESULTS: Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively. CONCLUSIONS: Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.