This study pictures the humoral response of 100 vaccinees to Pfizer/BioNTech COVID-19 vaccine over a year, with particular focus on the influence of a booster shot administered around 10 months after the primary immunization. The response to the vaccination was assessed with Diasorin’s SARS-CoV-2 TrimericSpike IgG. Abbott’s SARS-CoV-2 Nucleocapsid IgG immunoassay was used to identify SARS-CoV-2 contact, even asymptomatic. In contrast to the gradual decline of the anti-spike IgG between 30 and 240 days after the first dose, an increase was noted between days 240 and 360 in the whole cohort. However, a statistically significant rise was seen only in boosted individuals, and this effect of the booster decreased over time. An increase was also observed in non-boosted but recently infected participants and a decrease was reported in non-boosted, non-infected subjects. These changes were not statistically significant. On day 360, a percentage of new SARS-CoV-2 infections was statistically lower in the boosted vs. non-boosted subgroups. The booster immunization is the most efficient way of stimulating production of anti-spike, potentially neutralizing antibodies. The response is additionally enhanced by the natural contact with the virus. Individuals with a low level of anti-spike antibodies may benefit the most from the booster dose administration.