Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors

被引：351

作者：

Bonsignori, Mattia ^{[1
]}

Hwang, Kwan-Ki

Chen, Xi

Tsao, Chun-Yen

Morris, Lynn ^{[6
]}

Gray, Elin ^{[6
]}

Marshall, Dawn J.

Crump, John A. ^{[2
,7
,8
,9
]}

Kapiga, Saidi H. ^{[10
]}

Sam, Noel E. ^{[8
]}

Sinangil, Faruk ^{[11
]}

Pancera, Marie ^{[12
]}

Yang Yongping ^{[12
]}

Zhang, Baoshan ^{[12
]}

Zhu, Jiang ^{[12
]}

Kwong, Peter D. ^{[12
]}

O'Dell, Sijy ^{[12
]}

Mascola, John R. ^{[12
]}

Wu, Lan ^{[12
]}

Nabel, Gary J. ^{[12
]}

Phogat, Sanjay ^{[13
]}

Seaman, Michael S. ^{[14
]}

Whitesides, John F.

Moody, M. Anthony

Kelsoe, Garnett ^{[4
]}

Yang, Xinzhen ^{[14
]}

Sodroski, Joseph ^{[15
]}

Shaw, George M. ^{[16
,17
]}

Montefiori, David C. ^{[3
]}

Kepler, Thomas B. ^{[5
]}

Tomaras, Georgia D. ^{[3
]}

Alam, S. Munir

Liao, Hua-Xin

Haynes, Barton F. ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Med, Duke Human Vaccine Inst, Durham, NC 27710 USA

[2] Duke Univ, Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Durham, NC 27710 USA

[3] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[4] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA

[5] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC 27710 USA

[6] Natl Inst Communicable Dis, Johannesburg, South Africa

[7] Duke Univ, Duke Global Hlth Inst, Durham, NC 27710 USA

[8] Kilimanjaro Christian Med Ctr, Moshi, Tanzania

[9] Tumaini Univ, Kilimanjaro Christian Med Coll, Moshi, Tanzania

[10] London Sch Hyg & Trop Med, London WC1, England

[11] Global Solut Infect Dis, San Francisco, CA USA

[12] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[13] IAVI, AIDS Vaccine Design & Dev Lab, Brooklyn, NY USA

[14] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA

[15] Dana Farber Canc Inst, Boston, MA 02115 USA

[16] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[17] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA

来源：

JOURNAL OF VIROLOGY | 2011年 / 85卷 / 19期

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; B-CELL RESPONSES; CRYSTAL-STRUCTURE; PG9; AFFINITY; BREADTH; BINDING; PG16; TRANSFORMATION;

D O I：

10.1128/JVI.05045-11

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B. 9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies.

引用

页码：9998 / 10009

页数：12

共 63 条

[1] The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes [J].