Self-replicating RNA nanoparticle vaccine elicits protective immune responses against SARS-CoV-2

Guibin Lin; Huan Yan; Jing Sun; Jincun Zhao; Yuan Zhang

Molecular Therapy: Nucleic Acids (Jun 2023)

Self-replicating RNA nanoparticle vaccine elicits protective immune responses against SARS-CoV-2

Guibin Lin,
Huan Yan,
Jing Sun,
Jincun Zhao,
Yuan Zhang

Affiliations

Guibin Lin: The Second Affiliated Hospital, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, Guangdong 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong 510006, China
Huan Yan: The Second Affiliated Hospital, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, Guangdong 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong 510006, China
Jing Sun: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
Jincun Zhao: State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China; Institute of Infectious Disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510060, China
Yuan Zhang: The Second Affiliated Hospital, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, Guangdong 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong 510006, China; Corresponding author: Yuan Zhang, School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 511442, China.

Journal volume & issue: Vol. 32
pp. 650 – 666

Abstract

Read online

The creation of safe and effective vaccines that induce potent cellular and humoral immune responses against SARS-CoV-2 is urgently needed to end the global COVID-19 epidemic. Here, we developed an alphavirus-derived self-replicating RNA (repRNA)-based vaccine platform encoding the receptor-binding domain (RBD) of SARS-CoV-2 spike glycoprotein. The repRNA triggers prolonged antigen expression compared with conventional mRNA due to the replication machinery of repRNA. To improve the delivery and vaccine efficacy of repRNA, we developed a self-assembling liposome-protamine-RNA (LPR) nanoparticle with highly efficient encapsulation and transfection of repRNA. LPR-repRNA vaccines substantially activated type I interferon response and innate immune signaling pathways. Subcutaneous immunization of LPR-repRNA-RBD led to prolonged antigen expression, stimulation of innate immune cells, and induction of germinal center response in draining lymph nodes. LPR-repRNA-RBD induced antigen-specific T cell responses and skewed cellular immunity toward an effector memory CD8+ T cell response. Immunizations with LPR-repRNA-RBD triggered the production of anti-RBD IgG antibodies and induced neutralizing antibody response against SARS-CoV-2 pseudovirus. LPR-repRNA-RBD vaccines reduced SARS-CoV-2 infection and lung inflammation in mice. Altogether, these data suggest that the LPR-repRNA platform can be a promising avenue for COVID-19 vaccine development.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

About the journal

Abstract

Keywords