Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine.

ABSTRACT

BACKGROUND: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. METHODS: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. FINDINGS: After eight months from the second dose, IgG decreased in both serum (T2GMC 23,838.5 ng/ml; T3GMC 1473.8 ng/ml) and saliva (T2GMC 12.9 ng/ml; T3GMC 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC 48.6 ng/ml; T3GMC 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC 0.06 ng/ml; T3GMC 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both 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 a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction 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 of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy.