Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary neutralizing mucosal component of immunity, emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate that these IgAs mediate neutralization. RBD-targeting IgAs were found to associate with the secretory component, indicating their bona fide transcytotic origin and their polymeric multivalent nature. The mechanistic understanding of the high neutralizing activity provided by mucosal IgA, acting at the first line of defense, will advance vaccination design and surveillance principles and may point to novel treatment approaches and new routes of vaccine administration and boosting.

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Summary The growth promoting properties of ascitic fluids, cyst fluids and peritoneal fluids from patients with ovarian malignancy, benign ovarian tumours and non-tumour related gynaecological conditions have been investigated using an ovarian carcinoma cell line (OAW 42) (La Rocca & Rheinwald, 1985). Materials and methods Patient groupsAscitic fluids were collected from ovarian cancer patients (n = 42), non-ovarian cancer patients (n = 13), non-tumour patients (n = 4) and one patient with a benign ovarian tumour. Peritoneal fluids were collected from gynaecology patients undergoing laporotomy or laporoscopy for nontumour related conditions (n = 15), second-look laporotomies in ovarian cancer patients (n = 5), patients with benign ovarian tumours (n = 8) and with malignant ovarian tumours (n = 10). Cyst fluids were collected from borderline tumours (n = 3), benign tumours (n = 23) and malignant tumours (n = 11). All fluids were collected without heparin, centrifuged at 3,000 r.p.m. for 15 min to remove cells, aliquotted and frozen at -20°C.

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Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable 'sterilizing immunity' at the mucosal level. Our study uncovers, strong neutralizing mucosal component (NT50 ≤ 50pM), emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the Receptor-Binding-Domain (RBD) of SARS-CoV-2 spike protein and demonstrate that these IgAs are key mediators of potent neutralization. RBD-targeting IgAs were found to associate with the Secretory Component, indicating their bona-fide transcytotic origin and their dimeric tetravalent nature. The mechanistic understanding of the exceptionally high neutralizing activity provided by mucosal IgA, acting at the first line of defence, will advance vaccination design and surveillance principles, pointing to novel treatment approaches, and to new routes of vaccine administration and boosting.

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