A broadly protective antibody that targets the flavivirus NS1 protein

doi:10.1126/science.abb9425

GSTDTAP > 气候变化

DOI	10.1126/science.abb9425
	A broadly protective antibody that targets the flavivirus NS1 protein
	Naphak Modhiran; Hao Song; Lidong Liu; Cheryl Bletchly; Lou Brillault; Alberto A. Amarilla; Xiaoying Xu; Jianxun Qi; Yan Chai; Stacey T. M. Cheung; Renee Traves; Yin Xiang Setoh; Summa Bibby; Connor A. P. Scott; Morgan E. Freney; Natalee D. Newton; Alexander A. Khromykh; Keith J. Chappell; David A. Muller; Katryn J. Stacey; Michael J. Landsberg; Yi Shi; George F. Gao; Paul R. Young; Daniel Watterson
	2021-01-08
发表期刊	Science
出版年	2021
英文摘要	Flaviviruses are a group of RNA viruses that include the human pathogens dengue virus, Zika virus, and West Nile virus. The envelope protein (E) on the virus surface has been the target of vaccine development, but problems have arisen with antibodies against E, leading to enhanced infection. Now, Modhiran et al. and Biering et al. describe two different antibodies that bind to the flavivirus NS1 protein and prevent it from disrupting epithelial cells, which is associated with severe disease. Both antibodies cross-react with multiple flavivirus NS1 proteins. The antibodies reduce viremia and increase survival in mouse models of flavivirus disease. Both papers include structures of NS1 bound to an antibody, which give insight into the protective mechanism. Science , this issue p. [190][1], p. [194][2] There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development. [1]: /lookup/doi/10.1126/science.abb9425 [2]: /lookup/doi/10.1126/science.abc0476
领域	气候变化 ; 资源环境
URL	查看原文
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/310452
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Naphak Modhiran,Hao Song,Lidong Liu,et al. A broadly protective antibody that targets the flavivirus NS1 protein[J]. Science,2021.
APA	Naphak Modhiran.,Hao Song.,Lidong Liu.,Cheryl Bletchly.,Lou Brillault.,...&Daniel Watterson.(2021).A broadly protective antibody that targets the flavivirus NS1 protein.Science.
MLA	Naphak Modhiran,et al."A broadly protective antibody that targets the flavivirus NS1 protein".Science (2021).