Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2

Objectives This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity. Methods Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day90, Day180, 28 days after 3rd vaccination (Day251), Day365, and prior to 4th vaccination (Day535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day365, PCR+ after Day365) on anti-spike IgG trajectories. Results 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, p=<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity. Conclusion Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.