Booster doses of the SARS-CoV-2 vaccine have been recommended to improve and prolong immunity, address waning immunity over time, and contribute to the control of the COVID-19 pandemic. A heterologous booster vaccine strategy may offer advantages over a homologous approach. To compare the immunogenicity of two doses of BNT162b2 mRNA COVID-19 vaccine with a ChAdOx1-S booster dose, immunoglobulin G (IgG) anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody titers (Ab) were compared over 1 year and post-booster vaccination. Results showed that, at 3- to 9-month assessments in vaccinated subjects, an-ti-N Ab were undetectable in participants with no history of COVID-19. In contrast, anti-S Ab measurements were lower than those with COVID-19, and a decrease was observed during the 9 months of observation. After booster vaccination, no differences were found in anti-S between participants who reported a history of COVID-19 and those who did not. Anti-S levels were higher after booster vaccination measurement vs. at 9 months in participants with COVID-19 and without COVID-19, i.e., independent of an infection history. Vaccine administration elicited a response of higher anti-S IgG levels in those infected before vaccination, although levels decreased during the first nine months. IgG anti-N titers were higher in participants with a history of declared infection and who were asymptomatic. The ChAdOx1-S booster increased anti-S Ab levels in participants regardless of whether they had been infected or not to a significantly higher value than with the first two vaccines. These findings underscore the importance of booster vaccination in eliciting a robust and sustained immune response against COVID-19, regardless of the prior infection status.