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

Yaniv Lustig, Tal Gonen, Lilac Meltzer, Mayan Gilboa, Victoria Indenbaum, Carmit Cohen, Sharon Amit, Hanaa Jaber, Ram Doolman, Keren Asraf, Carmit Rubin, Ronen Fluss, Ella Mendelson, Laurence Freedman, Gili Regev-Yochay*, Yitshak Kreiss

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)940-946
Number of pages7
JournalNature Immunology
Volume23
Issue number6
DOIs
StatePublished - Jun 2022

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