A single immunization with core-shell structured lipopolyplex mRNA vaccine against rabies induces potent humoral immunity in mice and dogs.

Abstract	The persistence and clinical consequences of rabies virus (RABV) infection have prompted global efforts to develop a safe and effective vaccines against rabies. mRNA vaccines represent a promising option against emerging and re-emerging infectious diseases, gaining particular interest since the outbreak of COVID-19. Herein, we report the development of a highly efficacious rabies mRNA vaccine composed of sequence-modified mRNA encoding RABV glycoprotein (RABV-G) packaged in core-shell structured lipopolyplex (LPP) nanoparticles, named LPP-mRNA-G. The bilayer structure of LPP improves protection and delivery of RABV-G mRNA and allows gradual release of mRNA molecules as the polymer degrades. The unique core-shell structured nanoparticle of LPP-mRNA-G facilitates vaccine uptake and demonstrates a desirable biodistribution pattern with low liver targeting upon intramuscular immunization. Single administration of low-dose LPP-mRNA-G in mice elicited potent humoral immune response and provided complete protection against intracerebral challenge with lethal RABV. Similarly, single immunization of low-dose LPP-mRNA-G induced high levels of virus-neutralizing antibody titers in dogs. Collectively, our data demonstrate the potential of LPP-mRNA-G as a promising next-generation rabies vaccine used in human and companion animals.
Authors	Jiawu Wan, Jianmei Yang, Zongmei Wang, Ruizhong Shen, Chengguang Zhang, Yuntao Wu, Ming Zhou, Huanchun Chen, Zhen F Fu, Haiwei Sun, Yinglei Yi, Haifa Shen, Hangwen Li, Ling Zhao
Journal	Emerging microbes & infections (Emerg Microbes Infect) Vol. 12 Issue 2 Pg. 2270081 (Dec 2023) ISSN: 2222-1751 [Electronic] United States
PMID	37819147 (Publication Type: Journal Article)
Chemical References	Rabies Vaccines mRNA Vaccine Antibodies, Viral mRNA Vaccines RNA, Messenger
Topics	Dogs Animals Mice Humans Rabies (prevention & control) Rabies Vaccines Immunity, Humoral Tissue Distribution Antibodies, Viral mRNA Vaccines Rabies virus (genetics) Immunization RNA, Messenger (genetics)

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