China Ministry of Science and Technology Key Research and Development Program
2016YFC1200300
中国
引用
ジャーナル: Sci Transl Med / 年: 2016 タイトル: Molecular determinants of human neutralizing antibodies isolated from a patient infected with Zika virus. 著者: Qihui Wang / Huabing Yang / Xiaoqing Liu / Lianpan Dai / Tong Ma / Jianxun Qi / Gary Wong / Ruchao Peng / Sheng Liu / Junfu Li / Shihua Li / Jian Song / Jianying Liu / Jianhua He / Hui Yuan / ...著者: Qihui Wang / Huabing Yang / Xiaoqing Liu / Lianpan Dai / Tong Ma / Jianxun Qi / Gary Wong / Ruchao Peng / Sheng Liu / Junfu Li / Shihua Li / Jian Song / Jianying Liu / Jianhua He / Hui Yuan / Ying Xiong / Yong Liao / Jianhua Li / Jianping Yang / Zhou Tong / Bryan D Griffin / Yuhai Bi / Mifang Liang / Xiaoning Xu / Chuan Qin / Gong Cheng / Xinzheng Zhang / Peiyi Wang / Xiangguo Qiu / Gary Kobinger / Yi Shi / Jinghua Yan / George F Gao / 要旨: 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 ...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.
A: structural protein E B: structural protein E C: structural protein E D: strutural protein M E: strutural protein M F: strutural protein M H: Z23 Fab heavy chain L: Z23 Fab light chain M: Z23 Fab heavy chain N: Z23 Fab light chain
A: structural protein E B: structural protein E C: structural protein E D: strutural protein M E: strutural protein M F: strutural protein M H: Z23 Fab heavy chain L: Z23 Fab light chain M: Z23 Fab heavy chain N: Z23 Fab light chain
A: structural protein E B: structural protein E C: structural protein E D: strutural protein M E: strutural protein M F: strutural protein M H: Z23 Fab heavy chain L: Z23 Fab light chain M: Z23 Fab heavy chain N: Z23 Fab light chain
x 5
icosahedral pentamer
1.41 MDa, 50 ポリマー
分子量 (理論値)
分子数
合計 (水以外)
1,413,448
50
ポリマ-
1,413,448
50
非ポリマー
0
0
水
0
タイプ
名称
対称操作
数
identity operation
1_555
x,y,z
1
point symmetry operation
4
4
A: structural protein E B: structural protein E C: structural protein E D: strutural protein M E: strutural protein M F: strutural protein M H: Z23 Fab heavy chain L: Z23 Fab light chain M: Z23 Fab heavy chain N: Z23 Fab light chain
x 6
icosahedral 23 hexamer
1.7 MDa, 60 ポリマー
分子量 (理論値)
分子数
合計 (水以外)
1,696,137
60
ポリマ-
1,696,137
60
非ポリマー
0
0
水
0
タイプ
名称
対称操作
数
identity operation
1_555
x,y,z
1
point symmetry operation
5
5
登録構造と同一(異なる座標系)
icosahedral asymmetric unit, std point frame
タイプ
名称
対称操作
数
transform to point frame
1
6
A: structural protein E B: structural protein E C: structural protein E D: strutural protein M E: strutural protein M F: strutural protein M H: Z23 Fab heavy chain L: Z23 Fab light chain M: Z23 Fab heavy chain N: Z23 Fab light chain