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Science transl. Med. Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

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  • Science transl. Med. Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus

    Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus
    • Qihui Wang1,2,*,
    • Huabing Yang1,3,*,
    • Xiaoqing Liu4,*,
    • Lianpan Dai5,*,
    • Tong Ma1,3,
    • Jianxun Qi6,
    • Gary Wong2,6,7,
    • Ruchao Peng6,
    • Sheng Liu6,8,
    • Junfu Li1,
    • Shihua Li6,
    • Jian Song6,
    • Jianying Liu9,
    • Jianhua He10,
    • Hui Yuan4,
    • Ying Xiong4,
    • Yong Liao11,
    • Jianhua Li11,
    • Jianping Yang11,
    • Zhou Tong1,2,6,
    • Bryan D. Griffin12,13,
    • Yuhai Bi2,6,7,
    • Mifang Liang14,
    • Xiaoning Xu15,
    • Chuan Qin16,
    • Gong Cheng9,
    • Xinzheng Zhang17,18,
    • Peiyi Wang19,
    • Xiangguo Qiu12,13,
    • Gary Kobinger12,
    • Yi Shi2,6,
    • Jinghua Yan1,2,3,6,20,? and
    • George F. Gao2,5,6,7,8,14,21,22,?

    Stopping Zika virus in its tracks

    Zika virus is a global concern because of its association with fetal microcephaly and neurological complications, and there are no approved countermeasures. In new work, Wang et al. isolated 13 antibodies from a patient infected with Zika virus, two of which (Z3L1 and Z23) showed potent neutralizing activity without cross-reactivity to dengue virus strains 1 to 4. Moreover, the Z3L1 and Z23 antibodies conferred postexposure protection against Zika virus in a murine model. Structural studies indicated that the antibodies bound to different viral epitopes, suggesting that these antibodies could be used as a therapeutic cocktail.

    Abstract

    The 2015?2016 outbreak of Zika virus (ZIKV) disease has affected many countries and is a major public health concern. ZIKV is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent ZIKV infection. We report the isolation of 13 specific human monoclonal antibodies from a single patient infected with ZIKV. Two of the isolated antibodies (Z23 and Z3L1) demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. These two antibodies provided postexposure protection to mice in vivo. Structural studies revealed that Z23 and Z3L1 bound to tertiary epitopes in envelope protein domain I, II, or III, indicating potential targets for ZIKV-specific therapy. Our results suggest the potential of antibody-based therapeutics and provide a structure-based rationale for the design of future ZIKV-specific vaccines.





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