Divergent Requirement of Fc-Fc gamma Receptor Interactions for In Vivo Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies

doi:10.1128/JVI.02065-16

	Divergent Requirement of Fc-Fc gamma Receptor Interactions for In Vivo Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies
	Wang, Shuangshuang1,2 ; Ren, Huanhuan 1; Jiang, Wenbo 1; Chen, Honglin 3; Hu, Hongxing 1,4; Chen, Zhiwei 3; Zhou, Paul1,2
	2017-06
发表期刊	JOURNAL OF VIROLOGY (IF:4.0[JCR-2023],4.0[5-Year])
ISSN	0022-538X
卷号	91 期号:11
发表状态	已发表
DOI	10.1128/JVI.02065-16
摘要	Recent studies have shown that Fc-Fc gamma receptor (Fc gamma R) interactions are required for in vivo protection against influenza viruses by broadly reactive anti-hemagglutinin (HA) stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single-challenge virus strains, it remains unknown whether Fc-Fc gamma R interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS and whether the requirement is virus strain specific or epitope specific. In the present study, we therefore investigated the requirements for in vivo protection using two pan-H5 Abs, 65C6 and 100F4. We generated chimeric Abs, 65C6/IgG2a and 100F4/IgG2a, which preferentially engage activating Fc gamma Rs, and isogenic forms, 65C6/D265A and 100F4/D265A, which do not bind Fc gamma R. Virus neutralizing activity, binding, antibody-dependent cellular cytotoxicity (ADCC), and in vivo protection of these Abs were compared using three H5 strains, A/Shenzhen/406H/2006 (SZ06), A/chicken/Shanxi/2/2006 (SX06), and A/chicken/Netherlands/ 14015526/2014 (NE14). We found that all four chimeric Abs bound and neutralized the SZ06 and NE14 strains but poorly inhibited the SX06 strain. 65C6/IgG2a and 100F4/IgG2a, but not 65C6/D265A and 100F4/D265A, mediated ADCC against target cells expressing HA derived from all three virus strains. Interestingly, both 65C6/IgG2a and 65C6/D265A demonstrated comparable protection against all three virus strains in vivo; however, 100F4/IgG2a, but not 100F4/D265A, showed in vivo protection. Thus, we conclude that Fc-Fc gamma R interactions are required for in vivo protection by 100F4, but not by 65C6, and therefore, protection is not virus strain specific but epitope specific.
关键词	influenza viruses in vivo protection monoclonal antibodies
收录类别	SCI
语种	英语
资助项目	Ministry of Science and Technology in China[2013ZX10004003003003] ; Ministry of Science and Technology in China[2012AA02A404]
WOS研究方向	Virology
WOS类目	Virology
WOS记录号	WOS:000402166500024
出版者	AMER SOC MICROBIOLOGY
WOS关键词	CONSERVED NEUTRALIZING EPITOPE ; HUMAN MONOCLONAL-ANTIBODIES ; BINDING SITE ; A VIRUS ; EFFECTOR FUNCTIONS ; GLOBULAR HEAD ; HETEROSUBTYPIC ANTIBODY ; H5 HEMAGGLUTININ ; B VIRUSES ; RECOGNITION
原始文献类型	Article
通讯作者	Zhou, Paul
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1349
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_周保罗组生命科学与技术学院_硕士生
通讯作者	Zhou, Paul
作者单位	1.Chinese Acad Sci, Inst Pasteur Shanghai, Unit Antiviral Immun & Genet Therapy, Shanghai, Peoples R China 2.Shanghai Tech Univ, Shanghai, Peoples R China 3.Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China 4.European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany
第一作者单位	上海科技大学
通讯作者单位	上海科技大学
推荐引用方式 GB/T 7714	Wang, Shuangshuang,Ren, Huanhuan,Jiang, Wenbo,et al. Divergent Requirement of Fc-Fc gamma Receptor Interactions for In Vivo Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies[J]. JOURNAL OF VIROLOGY,2017,91(11).
APA	Wang, Shuangshuang.,Ren, Huanhuan.,Jiang, Wenbo.,Chen, Honglin.,Hu, Hongxing.,...&Zhou, Paul.(2017).Divergent Requirement of Fc-Fc gamma Receptor Interactions for In Vivo Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies.JOURNAL OF VIROLOGY,91(11).
MLA	Wang, Shuangshuang,et al."Divergent Requirement of Fc-Fc gamma Receptor Interactions for In Vivo Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies".JOURNAL OF VIROLOGY 91.11(2017).