Cited by 24Rabies epidemiology and controlVirology and Viral DiseasesAnimal Virus Infections Studies

Safety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques

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Li, Jianglong, Yu, Pengcheng, Liu, Qi, Xu, Long, Chen, Yan, Li, Yan, Zhang, Fan, Zhu, Wuyang +1 more·2024·npj Vaccines

Abstract

Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus’s glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.

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Authors
Li, J., Yu, P., Liu, Q., Xu, L., Chen, Y., Li, Y., Zhang, F., Zhu, W., & Peng, Y.
Affiliations
Chinese Center For Disease Control and Prevention (CN)
Corresponding author
  • Zhang, Fan
  • Zhu, Wuyang
  • Peng, Yucai
Venue
npj Vaccines
Published
2024-07-20
Volume
9
Issue
1
Pages
130-130
ISSN
2059-0105 (ISSN-L)
OpenAlex
W4400854461
Cited by
24
References
41
Citations by year
2026: 5 · 2025: 17 · 2024: 2
FWCI
5.56
Type
journal article
Language
en
Open access
Locations
  • npj Vaccines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Chinese Center for Disease Control and Prevention
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
rabies vaccine, mRNA vaccines, rabies virus glycoprotein, rabies prevention, pre-exposure prophylaxis, post-exposure prophylaxis, vaccine safety, vaccine efficacy, neutralizing antibodies, Th1 response, reproductive toxicity, chronic toxicity, cynomolgus macaques, dogs, rodents

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