Vaccines (Oct 2022)

Immunization with a Prefusion SARS-CoV-2 Spike Protein Vaccine (RBMRNA-176) Protects against Viral Challenge in Mice and Nonhuman Primates

  • Qinhai Ma,
  • Runfeng Li,
  • Jianmin Guo,
  • Man Li,
  • Lin Ma,
  • Jun Dai,
  • Yongxia Shi,
  • Jinlong Dai,
  • Yuankeng Huang,
  • Cailing Dai,
  • Weiqi Pan,
  • Huiling Zhong,
  • Hong Zhang,
  • Jian Wen,
  • Haoting Zhao,
  • Linping Wu,
  • Wei Yang,
  • Biliang Zhang,
  • Zifeng Yang

DOI
https://doi.org/10.3390/vaccines10101698
Journal volume & issue
Vol. 10, no. 10
p. 1698

Abstract

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There is an urgent need for a broad-spectrum and protective vaccine due to the emergence and rapid spreading of more contagious SARS-CoV-2 strains. We report the development of RBMRNA-176, a pseudouridine (Ψ) nucleoside-modified mRNA-LNP vaccine encoding pre-fusion stabilized trimeric SARS-CoV-2 spike protein ectodomain, and evaluate its immunogenicity and protection against virus challenge in mice and nonhuman primates. A prime-boost immunization with RBMRNA-176 at intervals of 21 days resulted in high IgG titers (over 1:819,000 endpoint dilution) and a CD4+ Th1-biased immune response in mice. RBMRNA-176 vaccination induced pseudovirus-neutralizing antibodies with IC50 ranging from 1:1020 to 1:2894 against SARS-CoV-2 spike pseudotyped wild-type and variant viruses, including Alpha, Beta, Gamma, and Kappa. Moreover, significant control of viral replication and histopathology in lungs was observed in vaccinated mice. In nonhuman primates, a boost given by RBMRNA-176 on day 21 after the prime induced a persistent and sustained IgG response. RBMRNA-176 vaccination also protected macaques against upper and lower respiratory tract infection, as well as lung injury. Altogether, these findings support RBMRNA-176 as a vaccine candidate for prevention of COVID-19.

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