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. Gatt; Saurabh Bhattacharya; Orly Zelig; Reuven Wiener; Dana G. Wolf; Hila Elinav; Jacob Strahilevitz; Dan Padawer; Leah Baraz; Alexander Rouvinski

doi:10.3389/fimmu.2022.933347

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. Gatt

Saurabh 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 journal › Article › peer-review

17 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 language	English
Article number	933347
Journal	Frontiers in Immunology
Volume	13
DOIs	https://doi.org/10.3389/fimmu.2022.933347
State	Published - 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.3389/fimmu.2022.933347

Cite this

Stolovich-Rain, M., Kumari, S., Friedman, A., Kirillov, S., Socol, Y., Billan, M., Pal, R. R., Das, K., Golding, P., Oiknine-Djian, E., Sirhan, S., Bejerano Sagie, M., Cohen-Kfir, E., Gold, N., Fahoum, J., Kumar, M., Elgrably-Weiss, M., Zhou, B., Ravins, M., ... Rouvinski, A. (2023). Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA. Frontiers in Immunology, 13, Article 933347. https://doi.org/10.3389/fimmu.2022.933347

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title = "Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces 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 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.",

keywords = "BNT162b2 vaccine, SARS-CoV-2 neutralizing Abs, mucosal immunity, secretory IgA, secretory component",

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

note = "Publisher Copyright: Copyright {\textcopyright} 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.",

year = "2023",

month = jan,

day = "30",

doi = "10.3389/fimmu.2022.933347",

language = "אנגלית",

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Stolovich-Rain, M, Kumari, S, Friedman, A, Kirillov, S, Socol, Y, Billan, M, Pal, RR, Das, K, Golding, P, Oiknine-Djian, E, Sirhan, S, Bejerano Sagie, M, Cohen-Kfir, E, Gold, N, Fahoum, J, Kumar, M, Elgrably-Weiss, M, Zhou, B, Ravins, M, Gatt, YE, Bhattacharya, S, Zelig, O, Wiener, R , Wolf, DG, Elinav, H, Strahilevitz, J, Padawer, D, Baraz, L & Rouvinski, A 2023, 'Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces neutralizing salivary IgA', Frontiers in Immunology, vol. 13, 933347. https://doi.org/10.3389/fimmu.2022.933347

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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 - Bejerano Sagie, Michal

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 - 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.

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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 - https://www.scopus.com/pages/publications/85148259517

U2 - 10.3389/fimmu.2022.933347

DO - 10.3389/fimmu.2022.933347

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C2 - 36798518

AN - SCOPUS:85148259517

SN - 1664-3224

VL - 13

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 933347

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

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