RT Journal Article
SR Electronic
T1 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
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.09.447656
DO 10.1101/2021.06.09.447656
A1 Jacob Pitcovski
A1 Nady Gruzdev
A1 Anna Abzach
A1 Chen Katz
A1 Ran Ben-Adiva
A1 Michal Brand Schwartz
A1 Itamar Yadid
A1 Hadar Haviv
A1 Irena Rapoport
A1 Itai Bloch
A1 Roy Shadmon
A1 Zohar Eitan
A1 Dalia Eliahu
A1 Talia Hilel
A1 Morris Laster
A1 Sigal Kremer Tal
A1 Tamara Byk Tennenbaum
A1 Ehud Shahar
YR 2021
UL http://biorxiv.org/content/early/2021/06/09/2021.06.09.447656.abstract
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.