Effectiveness of the third dose of BNT162b2 vaccine on neutralizing Omicron variant in the Japanese population

Abstract

Introduction: The vaccine against SARS-CoV-2 provides humoral immunity to fight COVID-19; however, the acquired immunity gradually declines. Booster vaccination restores reduced humoral immunity; however, its effect on newly emerging variants, such as the Omicron variant, is a concern. As the waves of COVID-19 cases and vaccine programs differ between countries, it is necessary to know the domestic effect of the booster.

Methods: Serum samples were obtained from healthcare workers (20-69 years old) in the Pfizer BNT162b2 vaccine program at the Toyama University Hospital 6 months after the second dose (6mA2D, n = 648) and 2 weeks after the third dose (2wA3D, n = 565). The anti-SARS-CoV-2 antibody level was measured, and neutralization against the wild-type and variants (Delta and Omicron) was evaluated using pseudotyped viruses. Data on booster-related events were collected using questionnaires.

Results: The median anti-SARS-CoV-2 antibody was >30.9-fold elevated after the booster (6mA2D, 710.0 U/mL [interquartile range (IQR): 443.0-1068.0 U/mL]; 2wA3D, 21927 U/mL [IQR: 15321.0->25000.0 U/mL]). Median neutralizing activity using 100-fold sera against wild-type-, Delta-, and Omicron-derived variants was elevated from 84.6%, 36.2%, and 31.2% at 6mA2D to >99.9%, 99.1%, and 94.6% at 2wA3D, respectively. The anti-SARS-CoV-2 antibody levels were significantly elevated in individuals with fever ≥37.5 °C, general fatigue, and myalgia, local swelling, and local hardness.

Conclusion: The booster effect, especially against the Omicron variant, was observed in the Japanese population. These findings contribute to the precise understanding of the efficacy and side effects of the booster and the promotion of vaccine campaigns.

Keywords: Anti-receptor binding domain antibody; BNT162b2; Booster; Neutralizing antibody; Omicron.

Fig. 1

The anti-RBD antibody levels before and after the booster Serum concentration of anti-RBD antibody at 6mA2D (n = 648, before the booster) and 2wA3D (n = 565, after the booster). Each dot represents an individual result.RBD, receptor-binding domain; 6mA2D, 6 months after the second dose; 2wA3D, 2 weeks after the third dose.****, p < 0.0001. Bars indicate the medians with interquartile ranges.

Fig. 2

Neutralizing activity against wild-type-, Delta- and Omicron-derived variants before and after the booster (A) Individual neutralizing activity against WT, Delta, and Omicron-derived variants at 6mA2D (n = 648) and 2wA3D (n = 565) using 100-fold diluted serum. The numbers at the top indicate the median neutralizing values of each group. (B) Neutralizing titration against WT, Delta, and Omicron-derived variants at 6mA2D (left) and 2wA3D (right) using the pooled serum. Dotted lines indicate interpolate standard curves.WT, wild-type; 6mA2D, 6 months after the second dose; 2wA3D, 2 weeks after the third dose.***, p < 0.001. Bars indicate the medians with interquartile ranges.

Fig. 3

Relationship of vaccine-induced antibody levels and vaccine-related symptoms after the booster in questionnaire-answered population (A) Anti-RBD antibody levels in individuals with systemic or local symptoms at 2wA3D (n = 510). (B) Relationship between anti-RBD antibody levels and specific symptoms including fever ≥37.5 °C, general fatigue, myalgia, swelling, and hardness at 2wA3D (n = 510).RBD, receptor-binding domain; 2wA3D, 2 weeks after the third dose.*, p < 0.05; **, p < 0.01; ***, p < 0.001. ****, p < 0.0001; ns, not significant. Bars indicate the medians with interquartile ranges.