Human Neutralizing Antibody Protects against Zika Virus in Mouse Models

Recent world attention has been drawn to a global Zika virus (ZIKV) outbreak and its link with devastating cases of microcephaly. Zika was first identified in the forests of Uganda in 1947, and infection was generally benign in humans. However, an emergent strain of ZIKV is far more virulent and causes a range of clinical anomalies since 2013.

 

ZIKV infection is spreading rapidly in the Americas after originating from an outbreak in Brazil. So far, more than 80 countries and territories have reported the circulation of this kind of mosquito-borne flavivirus. There is mounting concern about the association of ZIKV infection with congenital microcephaly, Guillain-Barré syndrome (GBS) and meningoencephalitis.

 

Neutralizing antibodies are the essential mediator of immunity against viral infection. Dr. XU Zhiheng’s group from the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, collaborated with Dr. ZHANG Linqi’s group from Tsinghua University, found that a single injection of human neutralizing antibody protects against Zika virus infection and microcephaly in the developing mouse embryos.

 

Dr. ZHANG Linqi’s group, collaborating with Fuchun Zhang’group from Guangzhou Eighth People’s Hospital, previously reported a panel of monoclonal antibodies (mAbs) derived from the longitudinal samples of a ZIKV-convalescent individual and characterized their neutralizing activities, epitope specificities, and development timeline over the course of infection (Yu et al., JCI 2017).

 

Recently, ZHANG Linqi’s group and XU Zhiheng’s group tested these human monoclonal antibodies in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine.

   

This work entitled “A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos” was on-line published in Cell Reports on May 1st, 2018 (DOI: https://doi.org/10.1016/j.celrep.2018.04.005).

 

This work is supported by grants from National Natural Science Foundation of China, Chinese Academy of Sciences and the Ministry of Science and Technology of China.

 

 

 

Contact:

Dr. XU Zhiheng