A mucosal antibody response is induced by intra-muscular SARS-CoV-2 mRNA vaccination

Mohamed, S. S.; Chao, G. Y. C.; Isho, B.; Zuo, M.; Nahass, G. R.; Salomon-Shulman, R. E.; Blacker, G.; Fazel-Zarandi, M.; Rathod, B.; Colwell, K.; Jamal, A.; Li, Z.; Quinn de Launay, K.; Takaoka, A.; Fahim, C.; Paterson, A.; Li, A.; Garnham-Takaoka, J.; Haq, N.; Barati, S.; Gilbert, L.; Green, K.; Mozafarihashjin, M.; Samaan, P.; Siqueira, W. L.; Mubareka, S.; Ostrowski, M. A.; Rini, J.; Rojas, O.; McGeer, A.; Weissman, I. L.; Caspi-Tal, M.; Strauss, S.; Gingras, A.-C.; Gommerman, J.

Vaccines against SARS-CoV-2 administered via the parenteral route (intra-muscular = i.m.) are effective at preventing COVID-19 in part by inducing neutralizing antibodies in the blood. The first line of defense against SARS-CoV-2 is in the upper respiratory tract, yet we know very little about whether COVID-19 vaccines induce immunity in this compartment, if at all. We analysed salivary antibodies against the SARS-CoV-2 Spike protein and its receptor binding domain (RBD) following 2 i.m. injections of either BNT162b2 or mRNA-1273 vaccines. Salivary anti-Spike/RBD IgG was detected after 1 dose and increased further after dose 2, reflecting the systemic immune response. Interestingly, salivary anti-Spike/RBD IgA associated with the secretory component (sIgA) was detected in nearly all vaccinated participants after one dose of mRNA vaccine, with anti-Spike sIgA diminishing after dose 2. Vaccination with ChAdOx1-S (Ad) followed by mRNA induced similar levels of salivary anti-Spike/RBD IgG and IgA, and both mRNA/mRNA and Ad/mRNA regimes provoked modest neutralizing capacity in this biofluid. Our results demonstrate that SARS-CoV-2 mRNA/mRNA and Ad/mRNA vaccination induces antibodies in the saliva, and in response to one dose of mRNA, a compartmentalized and transient antigen-specific sIgA response is generated that does not correlate with systemic immunity.