Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccineResearch in context
Lorenzo Azzi,
Daniela Dalla Gasperina,
Giovanni Veronesi,
Mariam Shallak,
Vittorio Maurino,
Andreina Baj,
Francesco Gianfagna,
Pierpaolo Cavallo,
Francesco Dentali,
Lucia Tettamanti,
Fabrizio Maggi,
Lorenzo Stefano Maffioli,
Angelo Tagliabue,
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
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
Vittorio Maurino
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Biotechnologies and Life Sciences, 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, Naples, Italy
Pierpaolo Cavallo
Department of Physics, University of Salerno, Fisciano (SA), Italy; Institute for Complex Systems, National Research Council, Rome, Italy
Francesco Dentali
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Lucia Tettamanti
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Biotechnologies and Life Sciences, University of Insubria, Varese, Italy
Fabrizio Maggi
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy
Lorenzo Stefano Maffioli
Chief Medical Officer, Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Varese, Italy
Angelo Tagliabue
Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, 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; Corresponding author. Laboratory of General Pathology and Immunology “Giovanna Tosi”, Department of Medicine and Surgery, University of Insubria, Via O. Rossi 9, 21100, Varese, Italy.
Summary: 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.
