A study conducted in England assessed the effectiveness of vaccines against symptomatic disease caused by the Omicron (B.1.1.529) and Delta (B.1.617.2) variants of SARS-CoV-2. The study used a test-negative case-control design to estimate vaccine effectiveness after two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccines, and after a booster dose of any of these vaccines. The study found that vaccine effectiveness against symptomatic disease was higher for the Delta variant than for the Omicron variant. For the Omicron variant, vaccine effectiveness after two doses of ChAdOx1 nCoV-19 dropped significantly after 20 weeks, while effectiveness after two doses of BNT162b2 was 65.5% at 2-4 weeks but dropped to 8.8% at 25 weeks or more. For ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased after a BNT162b2 booster but declined over time. For BNT162b2 primary course recipients, vaccine effectiveness increased after a BNT162b2 booster but also declined over time. For ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased after an mRNA-1273 booster but also declined over time. The study concluded that primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 provided limited protection against symptomatic disease caused by the Omicron variant. However, a booster dose of BNT162b2 or mRNA-1273 after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, although this protection waned over time. The study was funded by the UK Health Security Agency.A study conducted in England assessed the effectiveness of vaccines against symptomatic disease caused by the Omicron (B.1.1.529) and Delta (B.1.617.2) variants of SARS-CoV-2. The study used a test-negative case-control design to estimate vaccine effectiveness after two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccines, and after a booster dose of any of these vaccines. The study found that vaccine effectiveness against symptomatic disease was higher for the Delta variant than for the Omicron variant. For the Omicron variant, vaccine effectiveness after two doses of ChAdOx1 nCoV-19 dropped significantly after 20 weeks, while effectiveness after two doses of BNT162b2 was 65.5% at 2-4 weeks but dropped to 8.8% at 25 weeks or more. For ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased after a BNT162b2 booster but declined over time. For BNT162b2 primary course recipients, vaccine effectiveness increased after a BNT162b2 booster but also declined over time. For ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased after an mRNA-1273 booster but also declined over time. The study concluded that primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 provided limited protection against symptomatic disease caused by the Omicron variant. However, a booster dose of BNT162b2 or mRNA-1273 after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, although this protection waned over time. The study was funded by the UK Health Security Agency.