Authors: Louise White
Japanese encephalitis (JE) is one of the world’s most frequently occurring forms of viral encephalitis. There is currently no specific treatment for the infection, which has a mortality rate of 30–35% and can cause long-term disability. At present, WHO recommends Japanese encephalitis virus (JEV) vaccination as a treatment for JE in all areas where the disease is recognized as a significant risk to public health.
In a recent study published in PLoS Neglected Tropical Diseases, Guodong Liang and colleagues from the Chinese Center for Disease Control and Prevention (Beijing, China), carried out several experiments to test the efficacy of current JEV vaccines against an emerging G5 strain of the virus.
There are five different known genotypes of JE viruses, G1–G5. G5 was first discovered in 1951 but has not been epidemic over the last 60 years; however, it recently reemerged within the population in 2009 in both East Asia and Southern Asia, presenting potential new challenges for JE prevention and control.
Present vaccines against JE are based on G3 virus strains, which have repeatedly been shown to protect against G1–G4 strains. Despite this, their efficiency against the reemerging G5 strain has remained unclear.
Liang and his team initially used mice to test and compare the ability of G3 and G5 strains to cause disease. The researchers vaccinated the mice and tested whether or not they were protected against a dose of the virus that would have otherwise been lethal to an unvaccinated animal. The results showed that the G3-based vaccine protected all the mice against a lethal dose of G3 virus, however only 50% of mice infected with a lethal dose of G5 virus survived.
Subsequent experiments focused on human test subjects; the researchers first looked for neutralizing antibodies in vaccinated 2 year old children. Examining blood samples from 26 children that had been collected both before and 28 days after JE vaccination revealed that post-vaccination neutralizing antibodies against G3 strains were present in all children. Comparatively, only 35% of the children possessed antibodies that were capable of neutralizing G5 strains.
Finally, the researchers analyzed samples from 45 clinically diagnosed JE patients to see whether those infected with JEV naturally who had gone on to develop encephalitis possessed antibodies that could neutralize either the G3 or G5 strain of the virus. They discovered that while all of the patients had neutralizing antibodies against G3 strains, only 29 of the 45 patients (64%) had the ability to neutralize G5 strains.
These results indicate that existing vaccines provide only partial protection against G5 JEV strains instead of full protective immunity. This represents an early warning sign of a potential infectious disease crisis in South East Asia, with further research required concerning the development of vaccines that induce protective immunity of greater efficacy.
Sources: PLOS press release via EurekAlert!; Cao L, Fu S, Gao X et al. Low Protective Efficacy of the Current Japanese Encephalitis Vaccine against the Emerging Genotype 5 Japanese Encephalitis Virus. PLoS Negl. Trop. Dis. 10(5), e0004686 (2016).