AUTHOR=Stolovich-Rain Miri , Kumari Sujata , Friedman Ahuva , Kirillov Saveliy , Socol Yakov , Billan Maria , Pal Ritesh Ranjan , Das Kathakali , Golding Peretz , Oiknine-Djian Esther , Sirhan Salim , Sagie Michal Bejerano , Cohen-Kfir Einav , Gold Naama , Fahoum Jamal , Kumar Manoj , Elgrably-Weiss Maya , Zhou Bing , Ravins Miriam , Gatt Yair E. , Bhattacharya Saurabh , Zelig Orly , Wiener Reuven , Wolf Dana G. , Elinav Hila , Strahilevitz Jacob , Padawer Dan , Baraz Leah , Rouvinski Alexander TITLE=Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.933347 DOI=10.3389/fimmu.2022.933347 ISSN=1664-3224 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.