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Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer
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نویسنده
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derking r. ,ozorowski g. ,sliepen k. ,yasmeen a. ,cupo a. ,torres j.l. ,julien j.-p. ,lee j.h. ,van montfort t. ,de taeye s.w. ,connors m. ,burton d.r. ,wilson i.a. ,klasse p.-j. ,ward a.b. ,moore j.p. ,sanders r.w.
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منبع
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plos pathogens - 2015 - دوره : 11 - شماره : 3 - صفحه:1 -22
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چکیده
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The trimeric envelope (env) spike is the focus of vaccine design efforts aimed at generating broadly neutralizing antibodies (bnabs) to protect against hiv-1 infection. three recent developments have facilitated a thorough investigation of the antigenic structure of the env trimer: 1) the isolation of many bnabs against multiple different epitopes; 2) the generation of a soluble trimer mimic,bg505 sosip.664 gp140,that expresses most bnab epitopes; 3) facile binding assays involving the oriented immobilization of tagged trimers. using these tools,we generated an antigenic map of the trimer by antibody cross-competition. our analysis delineates three well-defined epitope clusters (cd4 binding site,quaternary v1v2 and asn332-centered oligomannose patch) and new epitopes at the gp120-gp41 interface. it also identifies the relationships among these clusters. in addition to epitope overlap,we defined three more ways in which antibodies can cross-compete: steric competition from binding to proximal but non-overlapping epitopes (e.g.,pgt151 inhibition of 8anc195 binding); allosteric inhibition (e.g.,pgt145 inhibition of 1nc9,8anc195,pgt151 and cd4 binding); and competition by reorientation of glycans (e.g.,pgt135 inhibition of cd4bs bnabs,and cd4bs bnab inhibition of 8anc195). we further demonstrate that bnab binding can be complex,often affecting several other areas of the trimer surface beyond the epitope. this extensive analysis of the antigenic structure and the epitope interrelationships of the env trimer should aid in design of both bnab-based therapies and vaccines intended to induce bnabs.
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آدرس
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department of medical microbiology,academic medical center,university of amsterdam,amsterdam, Netherlands, department of integrative structural and computational biology,the scripps research institute,la jolla,ca,united states,center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca, United States, department of medical microbiology,academic medical center,university of amsterdam,amsterdam, Netherlands, department of microbiology and immunology,weill medical college of cornell university,new york,ny, United States, department of microbiology and immunology,weill medical college of cornell university,new york,ny, United States, department of integrative structural and computational biology,the scripps research institute,la jolla,ca,united states,center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca, United States, department of integrative structural and computational biology,the scripps research institute,la jolla,ca,united states,center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca,united states,program in molecular structure and function,the hospital for sick children research institute and departments of biochemistry and immunology,university of toronto,toronto,on, Canada, department of integrative structural and computational biology,the scripps research institute,la jolla,ca,united states,center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca, United States, department of medical microbiology,academic medical center,university of amsterdam,amsterdam, Netherlands, department of medical microbiology,academic medical center,university of amsterdam,amsterdam, Netherlands, hiv-specific immunity section,laboratory of immunoregulation,national institute of allergy and infectious diseases,national institutes of health,bethesda,md, United States, center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca,united states,department of immunology and microbial science,the scripps research institute,la jolla,ca,united states,ragon institute of mgh,mit,and harvard,cambridge,ma, United States, department of integrative structural and computational biology,the scripps research institute,la jolla,ca,united states,center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca,united states,the skaggs institute for chemical biology,the scripps research institute,la jolla,ca, United States, department of microbiology and immunology,weill medical college of cornell university,new york,ny, United States, department of integrative structural and computational biology,the scripps research institute,la jolla,ca,united states,center for hiv/aids vaccine immunology and immunogen discovery,iavi neutralizing antibody center and the collaboration for aids vaccine discovery (cavd),the scripps research institute,la jolla,ca, United States, department of microbiology and immunology,weill medical college of cornell university,new york,ny, United States, department of medical microbiology,academic medical center,university of amsterdam,amsterdam,netherlands,department of microbiology and immunology,weill medical college of cornell university,new york,ny, United States
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Authors
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