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Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses

View ORCID ProfileTianyang Mao, View ORCID ProfileBenjamin Israelow, View ORCID ProfileAlexandra Suberi, Liqun Zhou, View ORCID ProfileMelanie Reschke, Mario A Peña-Hernández, Huiping Dong, Robert J. Homer, W. Mark Saltzman, View ORCID ProfileAkiko Iwasaki
doi: https://doi.org/10.1101/2022.01.24.477597
Tianyang Mao
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
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Benjamin Israelow
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
2Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA
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  • For correspondence: benjamin.goldman-israelow@yale.edu akiko.iwasaki@yale.edu
Alexandra Suberi
3Department of Biomedical Engineering, Yale University, New Haven, CT, USA
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Liqun Zhou
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
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Melanie Reschke
4Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA
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Mario A Peña-Hernández
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
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Huiping Dong
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
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Robert J. Homer
5Department of Pathology, Yale University School of Medicine, CT, USA
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W. Mark Saltzman
3Department of Biomedical Engineering, Yale University, New Haven, CT, USA
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Akiko Iwasaki
1Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
6Howard Hughes Medical Institute, Chevy Chase, MD, USA
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  • For correspondence: benjamin.goldman-israelow@yale.edu akiko.iwasaki@yale.edu
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Abstract

As the SARS-CoV-2 pandemic enters its third year, vaccines that not only prevent disease, but also prevent transmission are needed to help reduce global disease burden. Currently approved parenteral vaccines induce robust systemic immunity, but poor immunity at the respiratory mucosa. Here we describe the development of a novel vaccine strategy, Prime and Spike, based on unadjuvanted intranasal spike boosting that leverages existing immunity generated by primary vaccination to elicit mucosal immune memory within the respiratory tract. We show that Prime and Spike induces robust T resident memory cells, B resident memory cells and IgA at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, Prime and Spike enables induction of cross-reactive immunity against sarbecoviruses without invoking original antigenic sin.

One-sentence summary Broad sarbecovirus protective mucosal immunity is generated by unadjuvanted intranasal spike boost in preclinical model.

Competing Interest Statement

W.M.S. and A.I. are cofounders of Xanadu Bio. A.I., B.I., and T.M. are listed as inventors on patent applications relating to intranasal spike-based SARS-CoV-2 vaccines filed by the Yale University. A.I., W.M.S., B.I., T.M, A.S., and M.H. are listed as inventors on patent applications relating to intranasal PACE nanoparticle delivery-based vaccines filed by Yale University.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 26, 2022.
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Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses
Tianyang Mao, Benjamin Israelow, Alexandra Suberi, Liqun Zhou, Melanie Reschke, Mario A Peña-Hernández, Huiping Dong, Robert J. Homer, W. Mark Saltzman, Akiko Iwasaki
bioRxiv 2022.01.24.477597; doi: https://doi.org/10.1101/2022.01.24.477597
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Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses
Tianyang Mao, Benjamin Israelow, Alexandra Suberi, Liqun Zhou, Melanie Reschke, Mario A Peña-Hernández, Huiping Dong, Robert J. Homer, W. Mark Saltzman, Akiko Iwasaki
bioRxiv 2022.01.24.477597; doi: https://doi.org/10.1101/2022.01.24.477597

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