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Clinical Trial
. 2022 Jan:75:103788.
doi: 10.1016/j.ebiom.2021.103788. Epub 2021 Dec 23.

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients

Lorenzo Azzi  1 , Daniela Dalla Gasperina  2 , Giovanni Veronesi  3 , Mariam Shallak  4 , Giuseppe Ietto  2 , Domenico Iovino  2 , Andreina Baj  2 , Francesco Gianfagna  5 , Vittorio Maurino  2 , Daniele Focosi  6 , Fabrizio Maggi  2 , Marco Mario Ferrario  3 , Francesco Dentali  2 , Giulio Carcano  2 , Angelo Tagliabue  2 , Lorenzo Stefano Maffioli  7 , Roberto Sergio Accolla  4 , Greta Forlani  4
Affiliations
Clinical Trial

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients

Lorenzo Azzi et al. EBioMedicine. 2022 Jan.

Abstract

Background: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2.

Methods: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively.

Findings: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva.

Interpretation: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route.

Funding: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).

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

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Conflict of interest statement

Declaration of interests None to declare.

Figures

Fig. 1
Figure 1
Distribution of serum (panels A and B) and salivary (panels C and D) IgG and IgA, at different times, for all the recruited individuals and according to previous SARS-CoV-2 status at T0. In each group, the horizontal line represents the sample median, while the vertical line the interquartile range.
Fig. 2
Figure 2
Scatter-plot for salivary and serum IgG (panel A) and IgA (panel B) at different times according to previous SARS-CoV-2 status at T0.
Fig. 3
Figure 3
ROC curve for serum and salivary IgG to identify individuals with CLIA above 15 (A) and 90 (B) AU/ml
Fig. 4
Figure 4
Scatter-plot for salivary IgG and IgA among individuals with positive salivary NAb (n=15) at T2, according to previous SARS-CoV-2 status at T0.
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