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Comparisons among the different vaccines against SARS-CoV-2 are important to understand which type of vaccine provides more protection. This study aimed to evaluate the real-life efficacy through symptomatic infection and the humoral response of six different vaccines against SARS-CoV-2—BNT162b2, mRNA-1273, ChAdOx1-S, CoronaVac, Ad26.COV2, and Ad5-nCoV. This multicentric observational longitudinal study involved hospitals from Mexico and Brazil in which volunteers who received complete vaccination schemes were followed for 210 days after the last dose. SARS-CoV-2 Spike 1–2 IgG levels were taken before receiving the first vaccine, 21 days after each dose, and the last sample at six months (+/−1 month) after the last dose. A total of 1132 individuals exposed to five COVID-19 waves were included. All vaccines induced humoral responses, and mRNA vaccines had the highest antibody levels during follow-up. At six months, there was a decline in the SARS-CoV-2 Spike 1–2 IgG antibody titers of 69.5% and 36.4% in subjects with negative and positive history of infection respectively. Infection before vaccination and after complete vaccination scheme correlated with higher antibody titers. The predictors of infection were vaccination with CoronaVac compared to BNT162b2 and ChAdOx1-S. In the presence of comorbidities such as diabetes, rheumatoid arthritis, or dyslipidemia, CoronaVac lowered the risk of infection. [ABSTRACT FROM AUTHOR]