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

Emerg Microbes Infect. 2023 Dec;12(2):2270081. doi: 10.1080/22221751.2023.2270081. Epub 2023 Nov 22.

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.

Keywords: Lipopolyplex; RABV; dogs; humoral immunity; mRNA vaccine.

MeSH terms

  • Animals
  • Antibodies, Viral
  • Dogs
  • Humans
  • Immunity, Humoral
  • Immunization
  • Mice
  • RNA, Messenger / genetics
  • Rabies Vaccines*
  • Rabies virus* / genetics
  • Rabies* / prevention & control
  • Tissue Distribution
  • mRNA Vaccines

Substances

  • Rabies Vaccines
  • Antibodies, Viral
  • mRNA Vaccines
  • RNA, Messenger

Grants and funding

This study was supported by the Guangdong Major Project of Basic and Applied Basic Research (2020B0301030007 to Z.F.F). Project 2662023PY005 supported by the Fundamental Research Funds for the Central Universities. This work is also supported by the funding from the Science and Technology Commission of Shanghai Municipality (20S11909100 to H.W.L) and internal funding from Stemirna Therapeutics (SWP3007 to J.M.Y). The funders had no role in study design, data collection and analysis, publication decision, or manuscript preparation.