Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals

被引:155
作者
Tomaras, Georgia D. [1 ,11 ,12 ,13 ,14 ]
Binley, James M. [2 ]
Gray, Elin S. [3 ]
Crooks, Emma T. [2 ]
Osawa, Keiko [2 ]
Moore, Penny L. [3 ]
Tumba, Nancy [3 ]
Tong, Tommy [2 ]
Shen, Xiaoying [1 ,11 ,12 ,13 ,14 ]
Yates, Nicole L. [1 ,11 ,12 ,13 ,14 ]
Decker, Julie [5 ]
Wibmer, Constantinos Kurt [3 ]
Gao, Feng [1 ,11 ,12 ,13 ,14 ]
Alam, S. Munir [1 ,11 ,12 ,13 ,14 ]
Easterbrook, Philippa [5 ]
Karim, Salim Abdool [4 ]
Kamanga, Gift [6 ]
Crump, John A. [1 ,7 ,11 ,12 ,13 ,14 ]
Cohen, Myron [8 ]
Shaw, George M. [9 ]
Mascola, John R. [10 ]
Haynes, Barton F. [1 ,11 ,12 ,13 ,14 ]
Montefiori, David C. [1 ,11 ,12 ,13 ,14 ]
Morris, Lynn [3 ]
机构
[1] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA
[2] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA
[3] Natl Inst Communicable Dis, ZA-2131 Johannesburg, South Africa
[4] Univ KwaZulu Natal, ZA-4013 Durban, Kwazulu Natal, South Africa
[5] Kings Coll London, Sch Med & Dent, Western Educ Ctr, London SE5 9RJ, England
[6] Kamuzu Cent Hosp, Tidziwe Ctr, Lilongwe, Malawi
[7] Kilimanjaro Christian Med Ctr, Moshi, Tanzania
[8] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA
[9] Univ Alabama Birmingham, Div Hematol Oncol, Birmingham, AL 35294 USA
[10] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA
[11] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[12] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[13] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA
[14] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE PROTEINS; VIRAL ENVELOPE; ENV CLONES; HIV-1; GLYCOPROTEIN; BROAD; GP120;
D O I
10.1128/JVI.05363-11
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
A small proportion of HIV-infected individuals generate a neutralizing antibody (NAb) response of exceptional magnitude and breadth. A detailed analysis of the critical epitopes targeted by broadly neutralizing antibodies should help to define optimal targets for vaccine design. HIV-1-infected subjects with potent cross-reactive serum neutralizing antibodies were identified by assaying sera from 308 subjects against a multiclade panel of 12 "tier 2" viruses (4 each of subtypes A, B, and C). Various neutralizing epitope specificities were determined for the top 9 neutralizers, including clade A-, clade B-, clade C-, and clade A/C-infected donors, by using a comprehensive set of assays. In some subjects, neutralization breadth was mediated by two or more antibody specificities. Although antibodies to the gp41 membrane-proximal external region (MPER) were identified in some subjects, the subjects with the greatest neutralization breadth targeted gp120 epitopes, including the CD4 binding site, a glycan-containing quaternary epitope formed by the V2 and V3 loops, or an outer domain epitope containing a glycan at residue N332. The broadly reactive HIV-1 neutralization observed in some subjects is mediated by antibodies targeting several conserved regions on the HIV-1 envelope glycoprotein.
引用
收藏
页码:11502 / 11519
页数:18
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