Systemic and Mucosal Humoral Immune Response Induced by Three Doses of the BNT162b2 SARS-CoV-2 mRNA Vaccines

BNT162b2 (BioNTech/Pfizer) was the first SARS-CoV-2 mRNA vaccine approved by the European Medicines Agency. We monitored the long-term humoral responses of healthcare workers (HCWs) who received three vaccine doses. A total of 59 healthcare workers were studied: 47 were never SARS-CoV-2-infected (naive-HCWs), and 12 (infected-HCWs) recovered from COVID-19 before the first vaccine. Serum and saliva were collected at baseline (before the first dose), just before the second dose, 1, 3, 6, and 9 months after the second dose, and 10 days after the third vaccine. SARS-CoV-2-specific IgG and IgA were evaluated in serum and saliva, respectively, and the presence of neutralizing antibodies (NAb) was analyzed in serum. SARS-CoV-2-specific IgG peaked one month after the second vaccine in naive-HCWs but right before this timepoint in infected-HCWs. IgG titers significantly decreased during follow-up and at month 9 were still detectable in 50% of naive-HCWs and 90% of infected-HCWs. NAb were significantly decreased 6 months after the second vaccine in naive-HCWs and 9 months after this dose in infected-HCWs. Salivary SARS-CoV-2-specific IgA titers were significantly higher in infected-HCWs and were undetectable 9 months after the second vaccine in 43% of the naive-HCWs alone. The third vaccine greatly increased humoral IgG and mucosal IgA in both groups. Two BNT162b2 doses induced strong systemic and humoral immune responses; to note, these responses weakened over time, although they are more prolonged in individuals who had recovered from COVID-19. The third vaccine dose quickly boosts systemic and mucosal humoral responses.