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.
【저자키워드】 SARS-CoV-2, COVID-19 vaccine, variants, vaccine safety, antibody-dependent enhancement (ADE), nanoparticle vaccine, one-dose regimen, vaccine stability, 【초록키워드】 Vaccine, COVID-19 vaccine, vaccination, Vaccines, hamsters, SARS-COV-2 infection, body weight, SARS-CoV-2 virus, viral spread, immunization, Spike protein, Protein, serum, Viral, Receptor-binding domain, Viral load, mice, animals, RBD, nanoparticle, vaccine candidate, Trimeric spike protein, Neutralizing, hamster, S2 subunit, single dose, binding, Evidence, Safe, cross-reactive antibody, evidence of, glycine, golden hamster, weight loss, subunit, tissue damage, antigenic, viral loads, titre, position, ectodomain, trimeric spike, subunits, alleviation, Serum neutralizing antibody, display, immunized, PROTECT, resulting, caused, indicate, less, induce, significantly higher, suppressed, single-shot vaccine, the SARS-CoV-2 virus, 【제목키워드】 COVID-19, Vaccine, dose, PROTECT,