Temporal changes in spike IgG levels after two doses of BNT162b2 vaccine in Japanese healthcare workers: Do spike IgG levels at 3 months predict levels 6 or 8 months after vaccination?

BACKGROUND: Accurate timing of BNT162b2 boosters to prevent breakthrough infections of coronavirus disease 2019 (COVID-19) requires reliable estimates of immune status. We hypothesized that spike IgG levels at 3 months after two doses of the BNT162b2 vaccine might predict subsequent spike IgG levels. METHODS AND RESULTS: Spike IgG levels were tested at 3, 6, and 8 months after the second dose of the BNT162b2 vaccine in 251 Japanese health care workers (median age: 39 years, female: 187). The median level of spike IgG was 2,882 AU/mL at 3 months. This decreased to 875 AU/mL at 6 months and 579 AU/mL at 8 months. There were good correlations of log-transformed spike IgG levels between 3 and 6 months (r = 0.86) and between 3 and 8 months (r = 0.82). The correlation further improved after excluding three subjects who had possible COVID-19 infections (r = 0.91, r = 0.86). Log-transformed spike IgG levels at 6 or 8 months yields the following equation: log spike IgG at 6 (8) months = 0.92 (0.86) X log spike IgG at 3 months- 0.23 (0.18). Predicted spike IgG at 6 months of ≥ 300 or < 300 AU/mL had 98% sensitivity, 47% specificity, and 94% accuracy for discriminating subjects whose actual spike IgG titers at 6 months were above or below 300 AU/mL. Corresponding values of predicted spike IgG at 8 months were 97%, 70%, and 93%, respectively. CONCLUSIONS: We conclude that predictive formulae using spike IgG levels at 3 months after two-dose vaccination with BNT162b2 reliably estimate subsequent spike IgG levels up to 8 months and provide useful information in terms of vaccination booster timing.

Does reactogenicity after a second injection of the BNT162b2 vaccine predict spike IgG antibody levels in healthy Japanese subjects?

BACKGROUND: Adverse reactions are more common after the second injection of messenger RNA vaccines such as Pfizer/BioNTech's BNT162b2. We hypothesized that the degree and severity of reactogenicity after the second injection reflects the magnitude of antibody production against the SARS CoV-2 virus spike protein (spike IgG). METHODS AND RESULTS: Blood samples were obtained from 67 Japanese healthcare workers three weeks after the first injection and two weeks after the second injection of the BNT162b2 vaccine to measure spike IgG levels. Using questionnaires, we calculated an adverse event (AE) score (0-11) for each participant. The geometric mean of spike IgG titers increased from 1,047 antibody units (AU/mL) (95% confidence interval (95% CI): 855-1282 AU/mL) after the first injection to 17,378 AU/mL (95% CI: 14,622-20,663 AU/mL) after the second injection. The median AE score increased from 2 to 5. Spike IgG levels after the second injection were negatively correlated with age and positively correlated with spike IgG after the first injection. AE scores after the second injection were not significantly associated with log-transformed spike IgG after the second injection, when adjusted for age, sex, AE score after the first injection, and log-transformed spike IgG after the first injection. CONCLUSIONS: Although the sample size was relatively small, reactogenicity after the second injection may not accurately reflect antibody production.