Forlani. The booster elicited higher titres of both N-Shc IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9?ng/ml; IgA T4GMC: 187.5?ng/ml) and saliva (IgG T4GMC: 21.9?ng/ml; IgA T4GMC: 0.65?ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N?=?50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N?=?36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N?=?27, INH: 43.1%; Delta Plus N?=?24, INH: 35.2%; Omicron BA.1?N?=?4; INH: 4.7%). This was suggestive for any different behaviour of systemic immunity observed in serum with respect to mucosal immunity explained in saliva (Wald chi-square test, 3 df of conversation between variants and sample type?=?308.2, p?0.0001). Interpretation The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. Funding This work was funded by the Department of Medicine and Surgery, University or college of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy. Keywords: BNT162b2 mRNA vaccine, COVID-19, SARS-CoV-2, Saliva, IgA Research in context Evidence before this study On September 15th, 2022, we searched PubMed website for published peer-reviewed research articles written in English using the search terms BNT162b2 vaccine, salivary antibodies, and mucosal immunity. Several studies have shown that BNT162b2 COVID-19 mRNA vaccine induces neutralizing antibody responses in healthy adults after the main vaccination cycle and that the booster dose elicits a serologically detectable immune response that is even higher than the one recorded after the first two doses. However, only a few papers, including our previously published study, investigated the activation of a specific oral mucosal immunity after mRNA vaccination. They reported that 1C2 weeks after the main vaccination cycle vaccinated subjects experienced S-protein IgG antibodies in their saliva, while IgA were detected in a substantial proportion, but the neutralizing activity in the saliva was low, especially in those individuals that had been not previously exposed to SARS-CoV-2 natural contamination. To date, there are only few studies describing the oral mucosal immune response after the BNT162b2-booster vaccination. Assessing the mucosal immune response might provide data about vaccine efficacy against contamination and viral spread. This issue is crucial due to the emerging role of the SARS-CoV-2 variants of concern, including the Omicron variant. Added value of this Fasudil study This is one of the few reports assessing the Fasudil development of anti-S1-protein IgG and IgA antibodies and the neutralizing activity against both the Wuhan wild-type Receptor-Binding Domain name and the variants of concern (i.e., Delta, Delta Plus, and Omicron variants) in the saliva of individuals who underwent the BNT162b2-booster vaccination eight months Fasudil after the completion of the primary vaccination cycle. The follow up of the very same individuals who experienced participated to our study previously published in this journal allowed us to track closely the development of mucosal immunity from the primary vaccination cycle to the booster dose in a highly homogeneous sample. Our results demonstrate that although salivary IgA titres increase at 8 months from the primary BNT162b2-vaccination cycle, the booster elicits an effective mucosal immune response against the Wuhan-wildtype antigen which is dependent on salivary IgG exuded from your serum rather than salivary IgA, confirming and further extending our previous findings. In addition, the booster dose evokes a strong systemic immune response against the variants of concern, but fails to induce an effective mucosal immune response against them. Of notice, the neutralizing activity was dramatically reduced against the Omicron BA.1 variant. Implications of all the available evidence Together with the results of our previously published work, this study confirms that this intramuscular administration of the BNT162b2 vaccine elicits a strong systemic.