Hybrid immunity following SARS-CoV-2 infection and vaccination is associated with more sustained antibody levels, and lower reinfection risk

A decline in antibody levels against SARS-CoV-2 over time is expected and may lead to breakthrough infections (BTI; infection occurring after vaccination) and reinfections (infection occurring after recovery from a prior SARS-CoV-2 infection). This 12-month longitudinal study investigated the effects of antibody kinetics following SARS-CoV-2 vaccination and infection on the timing and likelihood of BTI or reinfection. Serum IgM, IgA, IgG, and neutralizing antibodies (NAb) against the ancestral SARS-CoV-2 variant were measured in a prospective cohort of 267 participants in Malaysia from March 2021 to May 2023, stratified by the order and timing of SARS-CoV-2 infection and vaccination relative to study enrollment. IgG levels following SARS-CoV-2 infection in individuals previously vaccinated with CoronaVac were higher up to Day 60 compared with those who received BNT162b2 or ChAdOX1 as their primary vaccination; however, antibody levels across vaccine platforms were not statistically different at six months and beyond post-vaccination. The risk of BTI was similar across vaccine platforms, whereas individuals with a history of SARS-CoV-2 infection prior to vaccination showed the lowest subsequent reinfection risk. Breakthrough infections in vaccinated individuals were associated with more sustained IgA, IgG, and NAb levels compared with vaccinated individuals without infection. Our results demonstrate that exposure sequence, rather than vaccine platform alone, is a key determinant of long-term antibody durability and reinfection risk, providing clinically interpretable evidence to inform vaccination strategies in the endemic phase of SARS-CoV-2.