As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1–66.7) to 96.3% (95% CI, 94.2–98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2–90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.

由于两剂信使 RNA (mRNA) 严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 疫苗方案的有效性随着时间的推移而降低，因此建议使用第三剂。在这里，我们在一项针对 12,413 名医护人员 (HCW) 的前瞻性队列研究中评估了第三剂 BNT162b2 疫苗的免疫原性、疫苗有效性和安全性。与第二剂相比，第三剂后抗 RBD 免疫球蛋白 G (IgG) 水平增加了 1.7 倍。亲和力从 61.1%（95% 置信区间 (CI)，56.1-66.7）增加到 96.3%（95% CI，94.2-98.5）导致中和滴度增加 6.1 倍。与 52 名匹配的对照相比，13 名第三剂 Delta 关注变异 (VOC) 突破病例的感染期体液标志物较低。第三剂相对于两剂的疫苗有效性为85。6%（95% CI，79.2–90.1）。没有报告严重的不良反应。这些结果表明，第三剂在 IgG 抗体的数量和质量上都优于第二剂，并且可以安全地增强对感染的保护。