BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and spread rapidly. The purpose of this study was to compare neutralizing antibodies (NAbs) following the original booster vaccine in convalescent and naive vaccinated individuals and in a third comparison group consisting of unvaccinated convalescent plasma donors.MethodsWe assessed NAbs before and 2 months after a booster vaccine in 68 adults who had completed the initial vaccine series for SARS-CoV-2. Of these subjects, 58 had no history of prior infection (naïve vaccinated group) and 10 had been infected with SARS-COV-2 prior to the completing the first vaccine series (convalescent vaccinated group). A third comparison group included unvaccinated convalescent plasma donors (n = 55) from an earlier study with NAbs assessed approximately 2 months after a positive test for SARS-CoV-2.ResultsPrior to the booster, convalescent vaccinated subjects had higher NAbs compared to naive vaccinated subjects (p = 0.02). Two months following the booster, NAbs increased in both vaccinated groups. The naive vaccinated group increased more than the convalescent vaccinated group (p = 0.02). NAbs in the naive vaccinated group were almost four times higher than NAbs in the 55 unvaccinated subjects, while the convalescent vaccinated group had levels 2.5 times higher p < 0.01.ConclusionNAbs in both vaccinated/boosted groups were significantly higher than in the convalescent unvaccinated group (p < 0.01). Our data indicates that subjects with a single infection with SARS-CoV-2 did not have the same levels of neutralizing antibodies that we observed in subjects who were either in the convalescent vaccinated or the naive vaccinated groups.