A paper by a team from QIMR Berghofer in npj viruses in May 2024 presents insights into the rare sub-type of the mosquito-borne Japanese encephalitis virus (JEV) behind an “unprecedented deadly outbreak” in Australia in 2022. QIMR Berghofer highlights the need for “vigilance and preparedness” in addressing mosquito-borne diseases and states that the team is deploying new tools to test vaccines against JEV.
JEV
The authors describe Japanese encephalitis virus (JEV) as a single-stranded, positive sense RNA virus from the Flaviviridae family. It is transmitted from amplifying hosts through mosquitoes to humans. Although infection is “usually asymptomatic”, encephalitis can develop in ≈1 in 250 people.
Around 30% of encephalitic cases become fatal, and between 30% and 50% of non-fatal encephalitic cases experience “persistent neurological symptoms” such as seizures, speech impediments, or paralysis. JEV is the “leading cause of viral encephalitis in Asia”, with ~70,000 cases and ~20,000 deaths each year. Although there are several available and effective vaccines, there are no specific licensed treatments.
JEV has five genotypes; these are “phylogenetically, antigenically, and geographically distinct”. The fourth, genotype 4, was the “least common genotype worldwide” until sequencing of a fatal JEV infection off the coast of Australia revealed that the virus belonged to this genotype. Following this, a “geographically widespread outbreak” across Australia was attributed to genotype 4.
The authors suspect that JEV “may become, or is already, endemic in Australia” as the Culex annulirostris mosquitoes are widespread. Two vaccines against JEV are licensed for use in Australia: IMOJEV (live attenuated) and JEspect (formalin inactivated). However, they are designed against a genotype 3 antigen.
The study
The study presents in vivo and in vitro characterisation of the genotype 4 JEV NSW/22 from the Australian outbreak, illustrating mouse models of infection and rare CNS neuropathological manifestations that “recapitulate many aspects of human and primate disease”. Investigating the effect of vaccination on this genotype, the researchers took serum from two human cohorts; all serum samples from both had a measurable 50% neutralisation titer.
The authors found that the IMOJEV vaccine is “likely to afford some protection” against this genotype. However, the implications of a “divergence of envelope protein amino acid sequences” on vaccine efficacy were unclear.
“Nevertheless, this provides a strong rationale for the development of updated JEV vaccines that use antigen sequences from currently circulating JEV strains.”
An argument for updating
QIMR Berghofer’s senior research officer, Dr Daniel Rawle, emphasised that “the more a virus mutates” and “deviates from established vaccine targets”, the “less optimal the vaccine responses are likely to be”. Dr Rawle believes that, like COVID-19 and influenza vaccines, JEV vaccines may need to be “continuously updated”.
“We don’t have targeted treatments for JEV, with brain infections particularly difficult to treat, so a vaccine would be a key defence against a disease with potentially fatal consequences.”
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