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 (T2_GMC: 23,838.5 ng/ml; T3_GMC: 1473.8 ng/ml) and saliva (T2_GMC: 12.9 ng/ml; T3_GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2_GMC: 48.6 ng/ml; T3_GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2_GMC: 0.06 ng/ml; T3_GMC: 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 T4_GMC: 98,493.9 ng/ml; IgA T4_GMC: 187.5 ng/ml) and saliva (IgG T4_GMC: 21.9 ng/ml; IgA T4_GMC: 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.

Keywords: BNT162b2 mRNA vaccine; COVID-19; IgA; SARS-CoV-2; Saliva.

Fig. 1

Distribution of serum (panels A and B) and salivary (panels C and D) IgG and IgA Ab, at different times, for all the recruited individuals and according to exposure to SARS-CoV-2 infection before the primary vaccination cycle. In each group, the horizontal line represents the sample median, while the vertical line the interquartile range. T2 = 14 days after the second dose; T3 = day of the booster dose; T4 = 14 days after the booster dose. Statistical analysis was reported in Table 1.

Fig. 2

Scatter-plot for salivary and serum IgG (panel A) and IgA (panel B) at different times. T2 = 14 days after the second dose; T3 = day of the booster dose; T4 = 14 days after the booster dose. Correlations between serum and salivary IgG Ab titres: T2: r = 0.295, p = 0.04; T3: r = 0.442, p = 0.0013; T4: r = 0.521, p = 0.0001. Correlations between serum and salivary IgA Ab titres: T2: r = 0.211, p = 0.15; T3: r = 0.172, p = 0.23; T4: r = 0.261, p = 0.07.

Fig. 3

Scatter-plot for salivary IgG ad IgA among individuals with positive salivary NAb (N = 36) at T4, according to exposure to SARS-CoV-2 during the follow-up after the booster dose. Spearman r: 0.523, p < 0.0001.

Fig. 4

Serum (orange) and salivary (light blue) NAb percentage distribution according to SARS-CoV-2 variant, among individuals showing salivary NAb against the Wuhan antigen at T4 (N = 36).