The human disease Japanese encephalitis (JE) can be prevented by vaccination, although it is not entirely clear if the emerging JEV G5 genotype can be controlled using the vaccine based on the G3 genotype. Consequently, we systematically compared G3 and G5 cross-neutralizing immune responses in vaccinated humans and, separately, cross-protective immune responses in mice using the current G3 JE vaccine to induce the immunity. Based on these results, we propose that the current JE vaccine derived from G3 JE virus (JEV) does not provide adequate levels of protection against the emerging G5 JEV genotype.

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