(1) Background: COVID-19 vaccination in Brazil has been performed mostly with CoronaVac (Sinovac), ChAdOx1-S (AstraZeneca-University of Oxford) and BNT162b2 (Pfizer-BioNTech) vaccines. The titers of IgG antibodies reactive to the SARS-CoV-2 spike protein correlate with vaccine efficacy. Studies comparing vaccine immunogenicity in a real-world scenario are lacking. (2) Methods: We performed a population-based study to analyze the immunoglobulin G response to different COVID-19 vaccines. Citizens older than 18 years (n = 2376) provided personal data, a self-declaration of any previous COVID-19 positive tests and information regarding COVID-19 vaccination: the vaccine popular name and the date of each dose. Blood samples were collected and the levels of IgG reactive to SARS-CoV-2 antigens were determined and compared between different vaccine groups. (3) Results: The seroconversion for anti-spike IgG achieved > 95% by February 2022 and maintained stable until June 2022. Higher anti-spike IgG titers were detected in individuals vaccinated with BNT162b2, followed by ChAdOx1-S and CoronaVac. The anti-spike IgG response was negatively correlated with age and interval after the second dose for the BNT162b2 vaccine. Natural infections boosted anti-spike IgG in those individuals who completed primary vaccination with ChAdOx1-S and CoronaVac, but not with BNT162b2. The levels of anti-spike IgG increased with the number of vaccine doses administered. The application of BNT162b2 as a 3rd booster dose resulted in high anti-spike IgG antibody titers, despite the type of vaccine used during primary vaccination. (4) Conclusions: Our data confirmed the effectiveness of the Brazilian vaccination program. Of the vaccines used in Brazil, BNT162b2 performed better to elicit anti-spike protein IgG after primary vaccination and as a booster dose and thus should be recommended as a booster whenever available. A continuous COVID-19 vaccination program will be required to sustain anti-spike IgG antibodies in the population.
