Induction of Antibodies in Rhesus Macaques That Recognize a Fusion-Intermediate Conformation of HIV-1 gp41

被引：62

作者：

Dennison, S. Moses ^{[1
]}

Sutherland, Laura L. ^{[1
]}

Jaeger, Frederick H. ^{[1
]}

Anasti, Kara M. ^{[1
]}

Parks, Robert ^{[1
]}

Stewart, Shelley ^{[1
]}

Bowman, Cindy ^{[1
]}

Xia, Shi-Mao ^{[1
]}

Zhang, Ruijun ^{[1
]}

Shen, Xiaoying ^{[1
]}

Scearce, Richard M. ^{[1
]}

Ofek, Gilad ^{[4
]}

Yang, Yongping ^{[4
]}

Kwong, Peter D. ^{[4
]}

Santra, Sampa ^{[2
]}

Liao, Hua-Xin ^{[1
]}

Tomaras, Georgia ^{[1
]}

Letvin, Norman L. ^{[2
]}

Chen, Bing ^{[3
]}

Alam, S. Munir ^{[1
]}

Haynes, Barton F. ^{[1
]}

机构：

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

[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Childrens Hosp,Dept Med, Boston, MA 02215 USA

[3] Harvard Univ, Childrens Hosp, Sch Med, Div Mol Med, Boston, MA 02115 USA

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

来源：

PLOS ONE | 2011年 / 6卷 / 11期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; AUTOREACTIVE B-CELLS; SURFACE-ANTIGEN; VACCINE DESIGN; 2F5; EPITOPE; MEMBRANE; ENVELOPE;

D O I：

10.1371/journal.pone.0027824

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A component to the problem of inducing broad neutralizing HIV-1 gp41 membrane proximal external region (MPER) antibodies is the need to focus the antibody response to the transiently exposed MPER pre-hairpin intermediate neutralization epitope. Here we describe a HIV-1 envelope (Env) gp140 oligomer prime followed by MPER peptide-liposomes boost strategy for eliciting serum antibody responses in rhesus macaques that bind to a gp41 fusion intermediate protein. This Env-liposome immunization strategy induced antibodies to the 2F5 neutralizing epitope (664)DKW residues, and these antibodies preferentially bound to a gp41 fusion intermediate construct as well as to MPER scaffolds stabilized in the 2F5-bound conformation. However, no serum lipid binding activity was observed nor was serum neutralizing activity for HIV-1 pseudoviruses present. Nonetheless, the Env-liposome prime-boost immunization strategy induced antibodies that recognized a gp41 fusion intermediate protein and was successful in focusing the antibody response to the desired epitope.

引用

页数：14

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