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Self-replicating RNA nanoparticle vaccine elicits protective immune responses against SARS-CoV-2
- Source :
- Molecular Therapy: Nucleic Acids, Vol 32, Iss , Pp 650-666 (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 21622531
- Volume :
- 32
- Issue :
- 650-666
- Database :
- Directory of Open Access Journals
- Journal :
- Molecular Therapy: Nucleic Acids
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8939241ba77647d383d6af0ef01aee67
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.omtn.2023.04.021