Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2-3 months after two ChAdOx1 doses, for 5-8 months after two BNT162b2 doses in those without prior infection and for 1-2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable. A large study in the United Kingdom shows that virus-specific antibody levels associated with at least 67% protection against SARS-CoV-2 Delta variant infection last longer after two doses of BNT162b2 vaccine than after two doses of ChAdOx1 vaccine in previously uninfected individuals.

Automated summary

This study investigated the antibody responses and protection following the second doses of ChAdOx1 or BNT162b2 vaccines against SARS-CoV-2 in the general population of the United Kingdom. The results showed significant boosting of anti-spike IgG antibody levels after the second doses of both vaccines, with BNT162b2 generating higher peak levels than ChAdOX1. Older individuals, males, and prior infection influenced the antibody levels. The levels of anti-spike IgG were associated with protection from infection after vaccination, and previous infection enhanced antibody peak levels and half-life. At least 67% protection against infection is estimated to last for 2-3 months after two ChAdOx1 doses, 5-8 months after two BNT162b2 doses in uninfected individuals, and 1-2 years after natural infection in unvaccinated individuals. A third booster dose may be necessary, prioritizing ChAdOx1 recipients and those more clinically vulnerable.