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

• DOI: 10.1016/j.omtn.2023.04.021
• Publication Date: 2023-04-23T01:46:48Z
• Authors: Guibin Lin; Huan Yan; Jing Sun; Jincun Zhao; Yuan Zhang
• Keywords: 2019-20 coronavirus outbreak; Coronavirus

The creation of safe and effective vaccines that induce potent cellular 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 receptor-binding domain (RBD) spike glycoprotein. repRNA triggers prolonged antigen expression compared with conventional mRNA due replication machinery repRNA. To improve delivery efficacy repRNA, a self-assembling liposome-protamine-RNA (LPR) nanoparticle highly efficient encapsulation transfection LPR-repRNA substantially activated type I interferon response innate signaling pathways. Subcutaneous immunization LPR-repRNA-RBD led expression, stimulation cells, induction germinal center in draining lymph nodes. induced antigen-specific T cell skewed immunity toward effector memory CD8+ response. Immunizations triggered production anti-RBD IgG antibodies neutralizing antibody pseudovirus. reduced infection lung inflammation mice. Altogether, these data suggest can be promising avenue for development.