ABSTRACT
Background: The long-term humoral immune response after vaccination varies between vaccines and is dependent on the accuracy of the antibody test. A better understanding of the vaccine immune response may help to define vaccination strategies against coronavirus disease 2019 (COVID-19). Objective: To investigate the long-term immunological response to CoronaVac vaccine and determinants of breakthrough COVID-19 infection. Methods: A long-term, prospective cohort study involving vaccinated adult and elderly subjects was conducted to investigate the presence of anti-RBD-specific immunoglobulin (Ig)G, anti-nucleocapsid IgG and anti-spike trimeric protein IgG. Antibody level dynamics and risk factors associated with breakthrough COVID-19 infection were investigated. Results: In total, 3902 participants were included in this study. Vaccination with two doses of CoronaVac and a booster dose increased the levels of anti-RBD-specific IgG, anti-nucleocapsid IgG and anti-spike trimeric IgG significantly. In adults, anti-nucleocapsid IgG and anti-spike trimeric IgG levels decreased significantly 7 months after the second dose. In adults and the elderly, the levels of anti-spike trimeric IgG and anti-RBD IgG decreased significantly 4 and 6 months after the booster dose, respectively. Previous exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and anti-spike trimeric IgG titres was independently associated with a lower probability of post-vaccination infection. Conclusions: A significant increase in antibody levels was found after two doses of CoronaVac and a booster dose. Antibody titres declined significantly 7 months post-vaccination in participants who did not receive a booster dose. Higher levels of antibodies and previous SARS-CoV-2 infection were associated with protection against breakthrough COVID-19.