A single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2

Qingrui Huang,Shuguang Tan,Kai Ji,Junfeng Hao,Jinghua Yan,Fengze Wang,George F Gao,Qihui Wang,Wenjie Tan,Zhou Tong,Baoying Huang,Siyu Tian

doi:10.1038/s41467-021-21037-2

Abstract

The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantage of versatility and rapid development, three SARS-CoV-2 mRNA vaccine candidates have entered clinical trials with a two-dose immunization regimen. However, the waning antibody response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concerns about a possible short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form that encoded the SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular responses, and conferred a near-complete protection against wild SARS-CoV-2 infection in the lungs of hACE2 transgenic mice. Noticeably, the high levels of neutralizing antibodies in BALB/c mice induced by mRNA-RBD vaccination were maintained for at least 6.5 months and conferred a long-term notable protection for hACE2 transgenic mice against SARS-CoV-2 infection in a sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge.

Highlights

The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority
Three SARS-CoV-2 mRNA vaccine candidates that have already advanced to clinical trials are mRNA-1273 encoding the viral S protein from Moderna[1,33], BNT162b1 expressing the receptor-binding domain (RBD) protein from BioNTech (Germany)[34], and ARCoV encoding the RBD protein developed by Abogen (China)[21]
The results demonstrated that the RBD was produced effectively and secreted into the supernatant of HEK293T cells (Fig. 1b)

Summary

Introduction

The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular responses, and conferred a nearcomplete protection against wild SARS-CoV-2 infection in the lungs of hACE2 transgenic mice. The high levels of neutralizing antibodies in BALB/c mice induced by mRNA-RBD vaccination were maintained for at least 6.5 months and conferred a long-term notable protection for hACE2 transgenic mice against SARS-CoV-2 infection in a sera transfer study. SARS-CoV-2 surface spike glycoprotein (S) can be cleaved into S1 and S2 subdomains, where the receptor-binding domain (RBD), located at the C-terminal of the S1 subdomain, engages human angiotensin-converting enzyme 2 (hACE2) as the receptor, and S2 mediates membrane fusion Both the full-length S protein and the RBD are capable of inducing highly potent neutralizing antibodies and cellular immunity[11,12,13,14]. We evaluated the protective efficacy of a single RBD-encoding mRNA immunization against wild SARS-CoV-2, investigated the kinetics of humoral response during 6.5 months following vaccination, and we demonstrated the long-term protection of immune sera for hACE2 transgenic mice from SARS-CoV-2 challenge

Methods

Results

Conclusion