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

Emerg Microbes Infect. 2021 Dec;10(1):2016-2029. doi: 10.1080/22221751.2021.1994354.

Abstract

ABSTRACTA 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.

Keywords: COVID-19 vaccine; SARS-CoV-2; antibody-dependent enhancement (ADE); nanoparticle vaccine; one-dose regimen; vaccine safety; vaccine stability; variants.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral / blood
  • Antibody Formation
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / immunology*
  • Cricetinae
  • Humans
  • Immunization
  • Immunization Schedule
  • Immunogenicity, Vaccine
  • Mesocricetus
  • Mice
  • Nanoparticles / chemistry*
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus
  • Vaccination
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus

Grant support

This study is partially supported by a fund from The University of Maryland Strategic Partnership (MPower) and the Institute for Bioscience and Biotechnology Research intramural startup fund (YL). This study is also partially supported by a fund from TEDCO (the Maryland Technology Development Corporation) (YW). With the mission to facilitate technology company growth in Maryland, TEDCO enhances economic development growth by fostering an inclusive entrepreneurial innovation ecosystem.