The Clalit Research Institute, in collaboration with researchers from Harvard University, analyzed one of the world’s largest integrated health record databases to examine the effectiveness of the third dose of the Pfizer/BioNTech BNT162B2 vaccine against the Delta variant of SARS-CoV-2. The study provides the largest peer-reviewed evaluation of the effectiveness of a third “booster” dose of a COVID-19 vaccine in a nationwide mass-vaccination setting. The study was conducted in Israel, an early global leader in third-dose COVID-19 vaccination rates.
Many countries are currently experiencing a resurgence of SARS-CoV-2 infections despite hitherto successful vaccination campaigns. This may be due to the greater infectiousness of the delta (B.1.617.2) variant of SARS-CoV-2, and to waning immunity of vaccines administered months earlier. In the face of the current resurgence, several countries are planning to administer a third booster dose of mRNA COVID-19 vaccine.

This study suggests that a third vaccine dose is effective in reducing severe COVID-19-related outcomes compared to individuals who have received two vaccine doses at least 5 months ago. It is the first to estimate the effectiveness of a third dose of an mRNA COVID-19 vaccine—BNT162b2 specifically—against severe outcomes with adjustment for various possible confounders, including comorbidities and behavioral factors. The study’s large size also allows a more precise assessment of the vaccine’s effectiveness across different time periods, different subpopulations (by sex, age and number of comorbidities), and different severe outcomes (which are rarer and thus require greater sample size). A recent clinical trial conducted by BioNTech included a smaller sample size and did not estimate the third-dose’s effects for more severe outcomes.