Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop.
Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop.
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DOI:
10.1016/j.immuni.2017.04.011
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发表时间:
2017-05-16
期刊:
影响因子:
32.4
通讯作者:
Binley JM
中科院分区:
文献类型:
--
作者:
Cale EM;Gorman J;Radakovich NA;Crooks ET;Osawa K;Tong T;Li J;Nagarajan R;Ozorowski G;Ambrozak DR;Asokan M;Bailer RT;Bennici AK;Chen X;Doria-Rose NA;Druz A;Feng Y;Joyce MG;Louder MK;O'Dell S;Oliver C;Pancera M;Connors M;Hope TJ;Kepler TB;Wyatt RT;Ward AB;Georgiev IS;Kwong PD;Mascola JR;Binley JM
Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain to side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design. To date, long recognition loops have been a hallmark of apex-targeting antibodies. Cale et al. identify a lineage of HIV-1 neutralizing antibodies that target the envelope trimer apex. The N90-VRC38 lineage uses a loop of average length - a feature that may make it a useful prototype for vaccine design.
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DOI:
10.1097/qad.0000000000000106
发表时间:
2014-01-14
期刊:
AIDS (London, England)
影响因子:
--
作者:
Hraber P;Seaman MS;Bailer RT;Mascola JR;Montefiori DC;Korber BT
通讯作者:
Korber BT
影响因子:
46.9
作者:
通讯作者:
--
影响因子:
3.7
作者:
Briney BS;Willis JR;Crowe JE Jr
通讯作者:
Crowe JE Jr
影响因子:
3
作者:
Huson, Daniel H.;Richter, Daniel C.;Rausch, Christian;Dezulian, Tobias;Franz, Markus;Rupp, Regula
通讯作者:
Rupp, Regula
影响因子:
64.5
作者:
de Taeye SW;Ozorowski G;Torrents de la Peña A;Guttman M;Julien JP;van den Kerkhof TL;Burger JA;Pritchard LK;Pugach P;Yasmeen A;Crampton J;Hu J;Bontjer I;Torres JL;Arendt H;DeStefano J;Koff WC;Schuitemaker H;Eggink D;Berkhout B;Dean H;LaBranche C;Crotty S;Crispin M;Montefiori DC;Klasse PJ;Lee KK;Moore JP;Wilson IA;Ward AB;Sanders RW
通讯作者:
Sanders RW