One dose of COVID-19 nanoparticle vaccine REVC-128 protects against SARS-CoV-2 challenge at two weeks post-immunization

• Published in: Emerging microbes & infections Vol. 10; no. 1; pp. 2016 - 2029
• Main Authors: Gu, Maggie, Torres, Jonathan L., Li, Yijia, Van Ry, Alex, Greenhouse, Jack, Wallace, Shannon, Chiang, Chi-I, Pessaint, Laurent, Jackson, Abigail M., Porto, Maciel, Kar, Swagata, Li, Yuxing, Ward, Andrew B., Wang, Yimeng
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2021; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Antibodies, Neutralizing; Antibodies, Viral - blood; Antibody Formation; antibody-dependent enhancement (ADE); COVID-19 - prevention & control; COVID-19 vaccine; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; Cricetinae; Humans; Immunization; Immunization Schedule; Immunogenicity, Vaccine; Mesocricetus; Mice; nanoparticle vaccine; Nanoparticles; Nanoparticles - chemistry; one-dose regimen; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Vaccination; vaccine safety; vaccine stability; variants; Viral Load; vaccine safety; SARS-CoV-2; nanoparticle vaccine; one-dose regimen; COVID-19 vaccine; antibody-dependent enhancement (ADE); variants; vaccine stability
• DOI: 10.1080/22221751.2021.1994354
• ISSN: 2222-1751

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.