TY - JOUR
T1 - Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA
AU - Stolovich-Rain, Miri
AU - Kumari, Sujata
AU - Friedman, Ahuva
AU - Kirillov, Saveliy
AU - Socol, Yakov
AU - Billan, Maria
AU - Pal, Ritesh Ranjan
AU - Das, Kathakali
AU - Golding, Peretz
AU - Oiknine-Djian, Esther
AU - Sirhan, Salim
AU - Sagie, Michal Bejerano
AU - Cohen-Kfir, Einav
AU - Gold, Naama
AU - Fahoum, Jamal
AU - Kumar, Manoj
AU - Elgrably-Weiss, Maya
AU - Zhou, Bing
AU - Ravins, Miriam
AU - Gatt, Yair E.
AU - Bhattacharya, Saurabh
AU - Zelig, Orly
AU - Wiener, Reuven
AU - Wolf, Dana G.
AU - Elinav, Hila
AU - Strahilevitz, Jacob
AU - Padawer, Dan
AU - Baraz, Leah
AU - Rouvinski, Alexander
N1 - Funding Information: We would like to thank for the generous support of the research from The Edmond and Benjamin de Rothschild Foundation. The research was also supported by grants from Israel Science Foundation (338/19), the Israel Ministry of Science and Technology (2020000381), and the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (AP08856811). We are grateful for the collaborative effort between different Faculties of the Hebrew University and Hadassah Medical Center for joint research. In particular, we would like to thank the following groups for contributing their time and resources and allocating their members for the research: Prof. Albert Taraboulos, Prof. Sigal Ben-Yehuda, Prof. Ilan Rosenshine, Prof. Emanuel Hanski, Prof. Yuval Dor, Prof. Hanah Margalit, Prof. Ora Furman, Prof. Shoshy Altuvia, and Dr. Netanel Tzarum. We are thankful to the following for help in assay developments; for helpful discussions, ideas, and comments on the research; and for help with writing the manuscript and interpreting the data: Prof. Albert Taraboulos, Prof. Herve (Hillel) Bercovier, Prof. Sigal Ben-Yehuda, Prof. Ilan Rosenshine, Prof. Zichria Zakay- Rones, Prof. Gilad Bachrach, Dr. Viviana Scaiewicz, Dr. Sharon Karniely, Prof. Moshe Kotler, Prof. Ran Nir-Paz, Dr. Netanel Tzarum, Dr. Michael Berger, Dr. Maayan Salton, Dr. Yoav Shaul, and Prof. Mark Saper. We would like to thank Prof. Moshe Kotler, Dr. Nir Paran, Dr. Moshe Dessau, and Prof. Amos Panet for the help with reagents and plasmids used for the initial establishment of a variety pseudotype assays. We are thankful to the Hadassah blood bank members and the Hadassah Clinical virology lab members. We would like to especially thank to all our cohort participants and to blood bank donors for their readiness and collaboration. Funding Information: We would like to thank for the generous support of the research from The Edmond and Benjamin de Rothschild Foundation. The research was also supported by grants from Israel Science Foundation (338/19), the Israel Ministry of Science and Technology (2020000381), and the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (AP08856811). We are grateful for the collaborative effort between different Faculties of the Hebrew University and Hadassah Medical Center for joint research. In particular, we would like to thank the following groups for contributing their time and resources and allocating their members for the research: Prof. Albert Taraboulos, Prof. Sigal Ben-Yehuda, Prof. Ilan Rosenshine, Prof. Emanuel Hanski, Prof. Yuval Dor, Prof. Hanah Margalit, Prof. Ora Furman, Prof. Shoshy Altuvia, and Dr. Netanel Tzarum. We are thankful to the following for help in assay developments; for helpful discussions, ideas, and comments on the research; and for help with writing the manuscript and interpreting the data: Prof. Albert Taraboulos, Prof. Herve (Hillel) Bercovier, Prof. Sigal Ben-Yehuda, Prof. Ilan Rosenshine, Prof. Zichria Zakay- Rones, Prof. Gilad Bachrach, Dr. Viviana Scaiewicz, Dr. Sharon Karniely, Prof. Moshe Kotler, Prof. Ran Nir-Paz, Dr. Netanel Tzarum, Dr. Michael Berger, Dr. Maayan Salton, Dr. Yoav Shaul, and Prof. Mark Saper. We would like to thank Prof. Moshe Kotler, Dr. Nir Paran, Dr. Moshe Dessau, and Prof. Amos Panet for the help with reagents and plasmids used for the initial establishment of a variety pseudotype assays. We are thankful to the Hadassah blood bank members and the Hadassah Clinical virology lab members. We would like to especially thank to all our cohort participants and to blood bank donors for their readiness and collaboration. 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.
PY - 2023/1/30
Y1 - 2023/1/30
N2 - 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.
AB - 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.
KW - BNT162b2 vaccine
KW - SARS-CoV-2 neutralizing Abs
KW - mucosal immunity
KW - secretory IgA
KW - secretory component
UR - http://www.scopus.com/inward/record.url?scp=85148259517&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2022.933347
DO - https://doi.org/10.3389/fimmu.2022.933347
M3 - Article
C2 - 36798518
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 933347
ER -
