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Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine

Jacob Pitcovski, Nady Gruzdev, Anna Abzach, Chen Katz, Ran Ben-Adiva, Michal Brand Schwartz, Itamar Yadid, Hadar Haviv, Irena Rapoport, Itai Bloch, Roy Shadmon, Zohar Eitan, Dalia Eliahu, Talia Hilel, Morris Laster, Sigal Kremer Tal, Tamara Byk Tennenbaum, Ehud Shahar
doi: https://doi.org/10.1101/2021.06.09.447656
Jacob Pitcovski
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
cTel-Hai Academic College, Upper Galilee, Israel
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Nady Gruzdev
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Anna Abzach
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Chen Katz
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Ran Ben-Adiva
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Michal Brand Schwartz
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Itamar Yadid
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
cTel-Hai Academic College, Upper Galilee, Israel
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Hadar Haviv
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Irena Rapoport
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Itai Bloch
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Roy Shadmon
bMigVax Ltd
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Zohar Eitan
bMigVax Ltd
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Dalia Eliahu
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Talia Hilel
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
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Morris Laster
bMigVax Ltd
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Sigal Kremer Tal
bMigVax Ltd
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Tamara Byk Tennenbaum
bMigVax Ltd
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Ehud Shahar
aMIGAL Research Institute in the Galilee Kiryat Shmona, Israel
cTel-Hai Academic College, Upper Galilee, Israel
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  • For correspondence: ehudsha@migal.org.il
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Abstract

The rapid spread of the COVID-19 pandemic, with its devastating medical and economic impacts, triggered an unprecedented race toward development of effective vaccines. The commercialized vaccines are parenterally administered, which poses logistic challenges, while adequate protection at the mucosal sites of virus entry is questionable. Furthermore, essentially all vaccine candidates target the viral spike (S) protein, a surface protein that undergoes significant antigenic drift. This work aimed to develop an oral multi-antigen SARS-CoV-2 vaccine comprised of the receptor binding domain (RBD) of the viral S protein, two domains of the viral nucleocapsid protein (N), and heat-labile enterotoxin B (LTB), a potent mucosal adjuvant. The humoral, mucosal and cell-mediated immune responses of both a three-dose vaccination schedule and a heterologous subcutaneous prime and oral booster regimen were assessed in mice and rats, respectively. Mice receiving the oral vaccine compared to control mice showed significantly enhanced post-dose-3 virus-neutralizing antibody, anti-S IgG and IgA production and N-protein-stimulated IFN-γ and IL-2 secretion by T cells. When administered as a booster to rats following parenteral priming with the viral S1 protein, the oral vaccine elicited markedly higher neutralizing antibody titres than did oral placebo booster. A single oral booster following two subcutaneous priming doses elicited serum IgG and mucosal IgA levels similar to those raised by three subcutaneous doses. In conclusion, the oral LTB-adjuvanted multi-epitope SARS-CoV-2 vaccine triggered versatile humoral, cellular and mucosal immune responses, which are likely to provide protection, while also minimizing technical hurdles presently limiting global vaccination, whether by priming or booster programs.

Highlights

  • MigVax-101 is a multi-epitope oral vaccine for SARS-CoV-2.

  • MigVax-101 elicits neutralizing IgG and IgA production and cellular responses in mice

  • MigVax-101 serves as an effective booster in rats to a parenteral anti-S1 vaccine.

Competing Interest Statement

The authors are in collaboration with MigVax Ltd in the development of its vaccine.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 09, 2021.
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Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine
Jacob Pitcovski, Nady Gruzdev, Anna Abzach, Chen Katz, Ran Ben-Adiva, Michal Brand Schwartz, Itamar Yadid, Hadar Haviv, Irena Rapoport, Itai Bloch, Roy Shadmon, Zohar Eitan, Dalia Eliahu, Talia Hilel, Morris Laster, Sigal Kremer Tal, Tamara Byk Tennenbaum, Ehud Shahar
bioRxiv 2021.06.09.447656; doi: https://doi.org/10.1101/2021.06.09.447656
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Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine
Jacob Pitcovski, Nady Gruzdev, Anna Abzach, Chen Katz, Ran Ben-Adiva, Michal Brand Schwartz, Itamar Yadid, Hadar Haviv, Irena Rapoport, Itai Bloch, Roy Shadmon, Zohar Eitan, Dalia Eliahu, Talia Hilel, Morris Laster, Sigal Kremer Tal, Tamara Byk Tennenbaum, Ehud Shahar
bioRxiv 2021.06.09.447656; doi: https://doi.org/10.1101/2021.06.09.447656

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