Construction of a recombinant vaccine expressing Nipah virus glycoprotein using the replicative and highly attenuated vaccinia virus strain LC16m8

PLoS Negl Trop Dis. 2023 Dec 15;17(12):e0011851. doi: 10.1371/journal.pntd.0011851. eCollection 2023 Dec.

Abstract

Nipah virus (NiV) is a highly pathogenic zoonotic virus that causes severe encephalitis and respiratory diseases and has a high mortality rate in humans (>40%). Epidemiological studies on various fruit bat species, which are natural reservoirs of the virus, have shown that NiV is widely distributed throughout Southeast Asia. Therefore, there is an urgent need to develop effective NiV vaccines. In this study, we generated recombinant vaccinia viruses expressing the NiV glycoprotein (G) or fusion (F) protein using the LC16m8 strain, and examined their antigenicity and ability to induce immunity. Neutralizing antibodies against NiV were successfully induced in hamsters inoculated with LC16m8 expressing NiV G or F, and the antibody titers were higher than those induced by other vaccinia virus vectors previously reported to prevent lethal NiV infection. These findings indicate that the LC16m8-based vaccine format has superior features as a proliferative vaccine compared with other poxvirus-based vaccines. Moreover, the data collected over the course of antibody elevation during three rounds of vaccination in hamsters provide an important basis for the clinical use of vaccinia virus-based vaccines against NiV disease. Trial Registration: NCT05398796.

MeSH terms

  • Animals
  • Cricetinae
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Henipavirus Infections* / prevention & control
  • Humans
  • Nipah Virus* / genetics
  • Vaccines, Synthetic / genetics
  • Vaccinia virus / genetics
  • Viral Vaccines* / genetics

Substances

  • Glycoproteins
  • Viral Vaccines
  • Vaccines, Synthetic

Associated data

  • ClinicalTrials.gov/NCT05398796

Grants and funding

This study was supported by the Japan Agency for Medical Research and Development (AMED) (Grant No JP21fk0108080 (MSH, SW) and 22wm0325002 (SW)), Takeda Science Foundation (Grant No 2017045212 (SW) and 2021181927 (SW), Kanae Foundation for the Promotion of Medical Science (46th Asia Oceania Research program, 46-3) (SW), and JSPS KAKENHI (Grant No JP22K06016) (SW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.