Sero-Molecular Epidemiology of Japanese Encephalitis in Zhejiang, an Eastern Province of China

Abstract

BackgroundSporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains.Methodology/Principal FindingsA total of 570 serum specimens were sampled from community population aged from 0 to 92 years old in Xianju county of Zhejiang Province in 2013–2014. Microseroneutralization test results were analyzed to estimate the population immunity and to observe antibody dynamics in vaccinated children. E genes of 28 JEV strains isolated in Zhejiang Province were sequenced for phylogenetic tree construction and molecular characteristics analysis with other selected strains. Positive JE neutralizing antibody rates were higher in residents ≥35 years old (81%~98%) and lower in residents <35 years old (0~57%). 7 or 8 years after the 2nd live attenuated vaccine dose, the antibodies against for 4 different strains with microseroneutralization test were decreased by 55%~73% on seropositive rates and by 25%~38% on GMTs respectively. JEV strains isolated in recent years were all grouped into GI, while those isolated in the 1980s belonged to GIII. On important amino acid sites related to antigenicity, there was no divergence between the Zhejiang JE virus strains and the vaccine strain (SA14-14-2).Conclusion/SignificancesJE neutralizing antibody positive rates increase in age ≥10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically.

Genotype I of Japanese Encephalitis Virus Virus-like Particles Elicit Sterilizing Immunity against Genotype I and III Viral Challenge in Swine

“…Several studies have focused on vaccine efficacy affected by genotype replacement. Overall results suggested that the GIII JEV vaccine might temporarily protect against GI virus infection, especially for travelers, but vaccine efficacy for long-term protection might be reduced in GI JEV epidemic or endemic countries or regions 18 – 25 .…”

“…Considerations of a next-generation JEV vaccine for sows might include an ability to block virus transmission and induce cross-protective activity against the currently dominant GI virus and other genotypic viruses, especially the co-circulating GIII virus in some JEV endemic regions 18 , 26 , 27 . Non-infectious and self-assembled virus-like particles (VLPs) can elicit protective immunity against viral infection and are a suitable vaccine candidate for many viruses including JEV 28 – 33 .…”

Rift Valley Fever Virus, Japanese Encephalitis Virus, and African Swine Fever Virus: Three Transboundary, Vector-Borne, Veterinary Biothreats With Diverse Surveillance, and Response Capacity Needs

“…Still, this type of platform could be a tool for screening serum samples of symptomatic individuals for multiple flaviviruses at once (87). Microseroneutralization tests have also been used in serosurveillance of JEV (88).…”

Japanese encephalitis vaccines: Immunogenicity, protective efficacy, effectiveness, and impact on the burden of disease

“…29 The results on the longevity of responses should be interpreted with caution since the outcome may depend on whether the study was conducted in a non-endemic or an endemic area. Seropositivity rates are known to increase significantly beyond 10-15 years of age in endemic areas, 167,[180][181][182] and an inverse correlation has been observed between an age of >5-6 years and the incidence of JE disease. 167 In addition, direct correlation between seropositivity rates and the incidence of JE in an area has also been documented.…”

“…Seropositivity rates are known to increase significantly beyond 10-15 years of age in endemic areas, 167,[180][181][182] and an inverse correlation has been observed between an age of >5-6 years and the incidence of JE disease. 167 In addition, direct correlation between seropositivity rates and the incidence of JE in an area has also been documented. 183 Furthermore, asymptomatic infections with other flaviviruses in endemic areas is expected to boost responses elicited by JE vaccination.…”