Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.
Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.
复制标题
人类抗V3 HIV单克隆抗体靶向的中和表位的计算预测。
DOI:
10.1371/journal.pone.0089987
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Cardozo T
中科院分区:
文献类型:
--
作者:
Shmelkov E;Krachmarov C;Grigoryan AV;Pinter A;Statnikov A;Cardozo T
The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs). Our data demonstrate that this approach, based purely on calculated energetics and 3D structural information, accurately predicts the presence of neutralization epitopes targeted by V3-specific mAbs 2219 and 447-52D in any HIV-1 strain. The method was used to calculate the range of conservation of these specific epitopes across all circulating HIV-1 viruses. Accurately identifying an Ab-targeted neutralization epitope in a virus by computational means enables easy prediction of the breadth of reactivity of specific mAbs across the diversity of thousands of different circulating HIV-1 variants and facilitates rational design and selection of immunogens mimicking specific mAb-targeted epitopes in a multivalent HIV-1 vaccine. The defined epitopes can also be used for the purpose of epitope-specific analyses of breakthrough sequences recorded in vaccine clinical trials. Thus, our study is a prototype for a valuable tool for rational HIV-1 vaccine design.
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影响因子:
1.5
作者:
Almond, David;Kimura, Tetsuya;Cardozo, Timothy
通讯作者:
Cardozo, Timothy
影响因子:
64.8
作者:
Barouch, Dan H.
通讯作者:
Barouch, Dan H.
DOI:
10.1097/qad.0b013e328342ff93
发表时间:
2011-03-13
期刊:
AIDS (London, England)
影响因子:
--
作者:
Hemelaar J;Gouws E;Ghys PD;Osmanov S;WHO-UNAIDS Network for HIV Isolation and Characterisation
通讯作者:
WHO-UNAIDS Network for HIV Isolation and Characterisation
DOI:
10.1056/nejmoa1113425
发表时间:
2012-04-05
期刊:
The New England journal of medicine
影响因子:
--
作者:
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者:
Kim JH
影响因子:
168.9
作者:
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者:
Robertson, Michael N.