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

• Published in: Nature communications Vol. 12; no. 1; pp. 776 - 10
• Main Authors: Huang, Qingrui, Ji, Kai, Tian, Siyu, Wang, Fengze, Huang, Baoying, Tong, Zhou, Tan, Shuguang, Hao, Junfeng, Wang, Qihui, Tan, Wenjie, Gao, George F., Yan, Jinghua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.02.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 45/62; 45/90; 49/109; 631/326/590/2293; 631/326/596/4130; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - immunology; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibody response; Cell Line; Clinical trials; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - genetics; COVID-19 Vaccines - immunology; Economic development; Female; Global health; Humanities and Social Sciences; Humans; Immunization; Infections; Lipids; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; mRNA; mRNA Vaccines; multidisciplinary; Neutralizing; Pandemics; Pandemics - prevention & control; Public health; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA, Viral - genetics; RNA, Viral - immunology; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Transgenic animals; Transgenic mice; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Viral diseases; Viral Envelope Proteins - immunology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21037-2

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. Several mRNA-based vaccines for SARS-CoV-2 are in late phase clinical development. Here, the authors show that a single immunization with a mRNA vaccine expressing SARS-CoV-2 spike RBD induces neutralizing antibodies that are maintained for at least 6.5 months and confer protection in a sera transfer study in mice.