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

Miri Stolovich-Rain, Sujata Kumari, Ahuva Friedman, Saveliy Kirillov, Yakov Socol, Maria Billan, Ritesh Ranjan Pal, Kathakali Das, Peretz Golding, Esther Oiknine-Djian, Salim Sirhan, Michal Bejerano Sagie, Einav Cohen-Kfir, Naama Gold, Jamal Fahoum, Manoj Kumar, Maya Elgrably-Weiss, Bing Zhou, Miriam Ravins, Yair E. GattSaurabh Bhattacharya, Orly Zelig, Reuven Wiener, Dana G. Wolf, Hila Elinav, Jacob Strahilevitz, Dan Padawer*, Leah Baraz*, Alexander Rouvinski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 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.

Original languageAmerican English
Article number933347
JournalFrontiers in Immunology
Volume13
DOIs
StatePublished - 30 Jan 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Stolovich-Rain, Kumari, Friedman, Kirillov, Socol, Billan, Pal, Das, Golding, Oiknine-Djian, Sirhan, Sagie, Cohen-Kfir, Gold, Fahoum, Kumar, Elgrably-Weiss, Zhou, Ravins, Gatt, Bhattacharya, Zelig, Wiener, Wolf, Elinav, Strahilevitz, Padawer, Baraz and Rouvinski.

Keywords

  • BNT162b2 vaccine
  • SARS-CoV-2 neutralizing Abs
  • mucosal immunity
  • secretory IgA
  • secretory component

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