Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose

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. Around the world, governments are urging populations to receive a third COVID-19 vaccine dose. Here, the authors compare immunogenicity, reactogenicity and effectiveness of a third dose versus the second dose of the BNT162b2 vaccine in a large group of healthcare workers in Israel.

Automated summary

This prospective cohort study assesses the immunogenicity, vaccine effectiveness, and safety of a third dose of the BNT162b2 vaccine. The study finds that the third dose of the vaccine demonstrates superior quantity and quality of IgG antibodies compared to the second dose, and safely enhances protection against infection.