PT  - JOURNAL ARTICLE
AU  - Jacob Pitcovski
AU  - Nady Gruzdev
AU  - Anna Abzach
AU  - Chen Katz
AU  - Ran Ben-Adiva
AU  - Michal Brand Schwartz
AU  - Itamar Yadid
AU  - Hadar Haviv
AU  - Irena Rapoport
AU  - Itai Bloch
AU  - Roy Shadmon
AU  - Zohar Eitan
AU  - Dalia Eliahu
AU  - Talia Hilel
AU  - Morris Laster
AU  - Sigal Kremer Tal
AU  - Tamara Byk Tennenbaum
AU  - Ehud Shahar
TI  - 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
AID  - 10.1101/2021.06.09.447656
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.09.447656
4099  - http://biorxiv.org/content/early/2021/06/09/2021.06.09.447656.short
4100  - http://biorxiv.org/content/early/2021/06/09/2021.06.09.447656.full
AB  - 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.HighlightsMigVax-101 is a multi-epitope oral vaccine for SARS-CoV-2.MigVax-101 elicits neutralizing IgG and IgA production and cellular responses in miceMigVax-101 serves as an effective booster in rats to a parenteral anti-S1 vaccine.Competing Interest StatementThe authors are in collaboration with MigVax Ltd in the development of its vaccine.