Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces robust neutralizing salivary IgA

Abstract

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.

Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

“…S1D). The lack of notable IgA production in the respiratory mucosal appeared to contrast with the detection of moderate but significant IgA responses in the saliva after mRNA vaccination (21,22). We also examined IgM in the blood and BAL and observed that, whereas detectable levels of IgM were present in the circulation of both the COVID-19-vaccinated group and prior infection cases, only prior infection elicited significantly elevated IgM responses in the BAL (fig.…”

Persistent Immune and Clotting Dysfunction Detected in Saliva and Blood Plasma after COVID-19

“…A recent study demonstrated that neutralizing activity of salivary IgA induced by SARS-CoV-2 infection was maintained up to 73 days after clinical symptom, but later time points (189-230 days) 67 . Salivary IgAs induced by vaccination with BNT162b2 showed similar kinetics in that the binding activity specific to the SARS-CoV-2 RBD peaked at 85-120 days post vaccination but diminished by 170-205 days 68 . Both studies demonstrated that the salivary IgAs secreted as in polymeric form (dimeric and tetrameric) were superior to confer neutralizing activity than IgGs.…”

Subclinical SARS-CoV-2 Infections and Endemic Human Coronavirus Immunity Shape SARS-CoV-2 Saliva Antibody Responses

“…There is overall agreement in the literature that mRNA vaccination induces IgG responses in saliva. [24][25][26][27][28][29] However, reports on saliva IgA responses after COVID-19 mRNA vaccines have varied. Several studies have reported detectable increases in saliva IgA after initial and/or booster vaccination with COVID-19 mRNA vaccines.…”

“…47,48 At least 2 studies that found increases in saliva IgA attempted to screen out unrecognized infections by testing for serum anti-SCV2 N IgG. 24,29 All rights reserved. No reuse allowed without permission.…”

“…Of those that have, most have found that COVID-19 mRNA vaccines induce spike-specific IgG antibodies in saliva. [24][25][26][27][28][29] In contrast, results regarding induction of saliva IgA by mRNA vaccines have been diverse, with some reporting measurable increases in saliva IgA after initial or booster vaccinations [24][25][26][27][28][29] and while other report minimal saliva IgA responses. 25,30,31 One particular challenge in addressing the knowledge gap of how well IM mRNA vaccines induce saliva antibodies is accounting for subclinical infections that may confound vaccine study results.…”