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The effects of Japanese encephalitis virus antibodies on Zika virus infection

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Abstract

Recently, Zika virus (ZIKV) has become more widespread, thus attracting global attention. The vaccine against Japanese encephalitis virus (JEV) is currently used in China, being included in planned immunisation regimes. Although ZIKV and JEV are closely related mosquito-borne Flaviviruses, and a complex cross-immune response within flaviviruses has been demonstrated, the effect of JEV vaccination on ZIKV infection has not been well described. Thus, this study aimed to explore the impact of different titres of anti-JEV antibodies (Abs) against ZIKV infection using sera from healthy human donors in Guangzhou and anti-JEV rabbit polyclonal antibodies (pAbs) in vitro and vivo. Human anti-JEV Ab titres were tested at decreasing concentrations as the age increased. A neutralising effect on ZIKV infection was observed when anti-JEV Ab titres in human sera or rabbit pAbs were high (the corresponding age was under 30 years). Even though a lower titre in human sera showed no apparent effect, whereas rabbit pAbs had an antibody-dependent enhancement(ADE)effect, we proved an ADE effect in vivo for the first time. This study suggests that individuals over 60 years of age are at high risk for JEV and ZIKV infection, and screening this age group for infection should strengthen. Furthermore, a deep exploration of the relationship between anti-JEV Abs and ZIKV infection is needed.

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Acknowledgements

We thank Guangzhou CDC for generously providing us with the volunteer sera samples and all the participants of this study and research institute staff for their technical support and contributions to this study.

Funding

This research was funded by the National Key R and D Program of China (grant no. 2018YFC1602206), National Natural Science Foundation of China (Grant no. 31470271, 81730110), Guangdong and Guangzhou Science and Technology Program key projects (Grant no. 2018B020207006 and 201803040006) and special fund for science and technology innovation cultivation of Guangdong university students in 2018 Climbing Program (pdjhb0103).

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Author notes

  1. Xiaoen He, Xinyue Lang, Jianhai Yu and Li Zhu contributed equally to this work.

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, 510515, China

    Xiaoen He, Xinyue Lang, Jianhai Yu, Li Zhu, Zhiran Qin, Xuling Liu, Pei Chen, Chengguqiu Dai, Tingting Chen, Xujuan Li, Yangyang Chen, Dongrui Zhou, Wanyi Fang, Weiwei Xiao, Bao Zhang, Qian Xie, Qinghua Wu & Wei Zhao

  2. Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmacy, Southern Medical University, Guangzhou, 510515, China

    Qinghua Wu & Wei Zhao

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  1. Xiaoen He
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Contributions

XH, XL and YJ conceived, designed and performed the experiments, analysed the data and wrote the manuscript; LZ, PC, CD, TC and WF performed the experiments and analysed the data; ZQ, XL, YC and DZ supervise the experiments and gave method advice. XL, WX, BZ and QX and provided technical guidance. WZ and QW played an important role in the study design, the decision to publish, and the preparation of the manuscript.

Corresponding authors

Correspondence to Qinghua Wu or Wei Zhao.

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Conflict of interest

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Ethical approval

All the persons involved, including parents of minors, have been acquired the purpose with the informed consent. The experimental procedures with blood samples were approved by the Institutional Ethics Review Board of Southern Medical University. Furthermore, the mice handling and experimental procedures were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Institutional Animal Care and Use Committees of the Southern Medical University (Permit Number: L2018018).

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He, X., Lang, X., Yu, J. et al. The effects of Japanese encephalitis virus antibodies on Zika virus infection. Med Microbiol Immunol 209, 177–188 (2020). https://doi.org/10.1007/s00430-020-00658-2

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