Mucosal immune response in BNT162b2 COVID-19 vaccine recipients
Lorenzo Azzi,
Daniela Dalla Gasperina,
Giovanni Veronesi,
Mariam Shallak,
Giuseppe Ietto,
Domenico Iovino,
Andreina Baj,
Francesco Gianfagna,
Vittorio Maurino,
Daniele Focosi,
Fabrizio Maggi,
Marco Mario Ferrario,
Francesco Dentali,
Giulio Carcano,
Angelo Tagliabue,
Lorenzo Stefano Maffioli,
Roberto Sergio Accolla,
Greta Forlani
Affiliations
Lorenzo Azzi
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy; Corresponding author at: ASST dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Via G. Piatti, 10, 21100, Varese, Italy.
Daniela Dalla Gasperina
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Giovanni Veronesi
Research Centre in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy
Mariam Shallak
Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Giuseppe Ietto
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Domenico Iovino
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Andreina Baj
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Francesco Gianfagna
Research Centre in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy; Mediterranea Cardiocentro, Napoli, Italy
Vittorio Maurino
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Daniele Focosi
North-Western Tuscany Blood Bank, Pisa University Hospital, Pisa, Italy
Fabrizio Maggi
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Marco Mario Ferrario
Research Centre in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy
Francesco Dentali
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Giulio Carcano
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Angelo Tagliabue
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Lorenzo Stefano Maffioli
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Varese, Italy
Roberto Sergio Accolla
Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Greta Forlani
Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Summary: 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).
