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ImportanceDuration of post-vaccination protection against COVID-19 in individuals is a critical issue, especially in nursing home (NH) residents, i.e. one of the most vulnerable populations. ObjectiveTo estimate the duration of the IgG(S) response to the mRNA BNT162b2 vaccine in NH residents with (COV-Yes) or without (COV-No) history of natural infection with SARS-CoV-2. Design, setting and participantsIgG(S) quantification was carried out at 3 different time periods following administration of the Pfizer BioNtech vaccine three then seven months after the 2nd dose and one month after the 3rd dose. 574 COV-Yes and COV-No NH residents were included in 2 cohorts Main (n=115, mean age 84 years) or Confirmatory (n=459, mean age 88 years). ExposureAll subjects received the BNT162b2 vaccine. Main outcomes and measurementsIgG(S) antibodies and seroneutralization capacity. ResultsNeutralization capacity was strongly correlated with IgG(S) levels (R276%) without any difference between COV-Yes and COV-No groups for the same levels of IgG(S). COV-Yes, compared to the COV-No subjects showed 5-fold and 15-fold higher IgG(S) titers 3 and 7 months after the 2nd dose, but less than 2-fold higher IgG(S) after the 3rd dose, due to a more pronounced effect of the 3rd dose in the COV-No group. These results were similar in both cohorts. After the 2nd dose, duration of assumed robust protection (IgG(S) >264 BAU/ml) was 2-fold higher in the COV-Yes vs. COV-No group 12.60 (10.69-14.44) vs 5.76 (3.91-8.64) months, and this advantage was mainly due to the higher IgG(S) titers after the 2nd dose and secondary to a slower decay over time. After the 3rd dose, duration (months) of robust protection was estimated at 11.87 (9.88-14.87) (COV-Yes) and 8.95 (6.85-11.04) (COV-No). Conclusions and relevanceIn old subjects living in NH, history of SARS-CoV-2 infection provides a clear advantage in the magnitude and duration of high IgG(S) titers following the 2nd dose. Importantly, the 3rd dose induces a much more pronounced IgG(S) response than the 2nd dose in COV-No subjects, the effect of which should be able to ensure in these subjects a prolonged protection against severe forms of COVID-19.