One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization
Author
Gu, MaggieTorres, Jonathan L
Li, Yijia
Ry, Alex Van
Greenhouse, Jack
Wallace, Shannon
Chiang, Chi-I
Pessaint, Laurent
Jackson, Abigail M
Porto, Maciel
Kar, Swagata
Li, Yuxing
Ward, Andrew B
Wang, Yimeng
Date
2021-10-15Journal
Emerging Microbes & InfectionsPublisher
Taylor and Francis Inc.Type
Article
Metadata
Show full item recordAbstract
A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain 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 titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by 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 SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protects hamsters against 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 history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.Keyword
Antibody-dependent Enhancement (ADE)COVID-19 vaccine
Nanoparticle vaccine
One-dose regimen
SARS-CoV-2
Vaccine safety
Vaccine stability
Variants
Identifier to cite or link to this item
http://hdl.handle.net/10713/17007ae974a485f413a2113503eed53cd6c53
10.1080/22221751.2021.1994354
Scopus Count
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