| Autor: |
Gu M; ReVacc Scientific, Frederick, MD, USA., Torres JL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Li Y; ReVacc Biotech, Frederick, MD, USA., Van Ry A; Bioqual, Rockville, MD, USA., Greenhouse J; Bioqual, Rockville, MD, USA., Wallace S; Experimental Pathology Laboratories, Sterling, VA, USA., Chiang CI; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA., Pessaint L; Bioqual, Rockville, MD, USA., Jackson AM; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Porto M; Bioqual, Rockville, MD, USA., Kar S; Bioqual, Rockville, MD, USA., Li Y; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.; Department of Microbiology and Immunology and Center of Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Wang Y; ReVacc Scientific, Frederick, MD, USA.; ReVacc Biotech, Frederick, MD, USA.; Institute for Bioscience and Biotechnology Research, Rockville, MD, USA. |
| Abstrakt: |
ABSTRACT A COVID-19 vaccine that can give early protection is needed to eliminate the viral spread efficiently. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomains with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titre at two weeks post-immunization. This is significantly higher than titre caused by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by a spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for the SARS-CoV-2 virus challenge was implemented two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against the SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ∼10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine to give the earliest protection against SARS-CoV-2 infection. |
