Abstract
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.
Funder
National Natural Science Foundation of China
Emergency Key Program of Guangzhou Laboratory
Guangdong Provincial Research Project for Prevention and Treatment of SARS-CoV-2
Guangdong Key Research and Development Plan
Traditional Chinese Medicine Bureau of Guangdong Province
Guangdong Provincial Department of Natural Resources project
Key Program “New Drug Creation” of Guangdong Key Research and Development Plan
Macao Science and Technology Development Fund
Guangzhou Science and technology planning project
Guangzhou Fundamental and Application Foundation Research Project
Youth Lift Project of China Association for Science and Technology
Subject
Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology
Cited by
3 articles.
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