It was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC.

Published randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, Delta, or Omicron) were searched until 4 March 2022. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1-estimate).

Eleven RCTs (161,388 participants), 20 cohort studies (52,782,321 participants), and 26 case-control studies (2,584,732 cases) were included. Eleven COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, BBIBP-CorV, SCB-2019, CVnCoV, and HB02) were included in this analysis. Full vaccination was effective against Alpha, Beta, Gamma, Delta, and Omicron variants, with VE of 88.0% (95% CI, 83.0–91.5), 73.0% (95% CI, 64.3–79.5), 63.0% (95% CI, 47.9–73.7), 77.8% (95% CI, 72.7–82.0), and 55.9% (95% CI, 40.9–67.0), respectively. Booster vaccination was more effective against Delta and Omicron variants, with VE of 95.5% (95% CI, 94.2–96.5) and 80.8% (95% CI, 58.6–91.1), respectively. mRNA vaccines (mRNA-1273/BNT162b2) seemed to have higher VE against VOC over others; significant interactions (p_interaction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. not mRNA vaccines).

Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta, Gamma, and Delta variants. Booster vaccination is more effective against Delta and Omicron variants. mRNA vaccines seem to have higher VE against Alpha, Beta, Gamma, and Delta variants over others.