Efficacy of genotype-matched vaccine against re-emerging genotype V Japanese encephalitis virus

Emerg Microbes Infect. 2024 Dec;13(1):2343910. doi: 10.1080/22221751.2024.2343910. Epub 2024 Apr 29.

Abstract

Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV), is a highly threatening disease with no specific treatment. Fortunately, the development of vaccines has enabled effective defense against JE. However, re-emerging genotype V (GV) JEV poses a challenge as current vaccines are genotype III (GIII)-based and provide suboptimal protection. Given the isolation of GV JEVs from Malaysia, China, and the Republic of Korea, there is a concern about the potential for a broader outbreak. Under the hypothesis that a GV-based vaccine is necessary for effective defense against GV JEV, we developed a pentameric recombinant antigen using cholera toxin B as a scaffold and mucosal adjuvant, which was conjugated with the E protein domain III of GV by genetic fusion. This GV-based vaccine antigen induced a more effective immune response in mice against GV JEV isolates compared to GIII-based antigen and efficiently protected animals from lethal challenges. Furthermore, a bivalent vaccine approach, inoculating simultaneously with GIII- and GV-based antigens, showed protective efficacy against both GIII and GV JEVs. This strategy presents a promising avenue for comprehensive protection in regions facing the threat of diverse JEV genotypes, including both prevalent GIII and GI as well as emerging GV strains.

Keywords: Japanese encephalitis virus; genotype V; neutralizing antibody; recombinant vaccine; bivalent vaccine.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Cholera Toxin / genetics
  • Cholera Toxin / immunology
  • Encephalitis Virus, Japanese* / classification
  • Encephalitis Virus, Japanese* / genetics
  • Encephalitis Virus, Japanese* / immunology
  • Encephalitis, Japanese* / immunology
  • Encephalitis, Japanese* / prevention & control
  • Encephalitis, Japanese* / virology
  • Female
  • Genotype*
  • Humans
  • Japanese Encephalitis Vaccines* / administration & dosage
  • Japanese Encephalitis Vaccines* / genetics
  • Japanese Encephalitis Vaccines* / immunology
  • Mice
  • Mice, Inbred BALB C
  • Vaccine Efficacy

Substances

  • Japanese Encephalitis Vaccines
  • Antibodies, Viral
  • Antigens, Viral
  • Cholera Toxin

Grants and funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant numbers: HV22C0250 and HV22C0259).