Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope

被引:57
作者
Arnold, Gail Ferstandig [1 ,2 ,3 ]
Velasco, Paola K. [1 ,2 ,3 ]
Holmes, Andrew K. [1 ,2 ,3 ]
Wrin, Terri [4 ]
Geisler, Sheila C. [1 ,2 ]
Phung, Pham [4 ]
Tian, Yu [2 ]
Resnick, Dawn A. [1 ,2 ]
Ma, Xuejun [1 ,2 ]
Mariano, Thomas M. [1 ,2 ]
Petropoulos, Christos J. [4 ]
Taylor, John W. [2 ]
Katinger, Hermann [5 ]
Arnold, Eddy [1 ,2 ,3 ]
机构
[1] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA
[2] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA
[3] Rutgers State Univ, Univ Med & Dent, New Jersey Mol Biosci Grad Program, Piscataway, NJ 08854 USA
[4] Monogram Biosci Inc, San Francisco, CA USA
[5] Univ Bodenkultur Wien, Inst Appl Microbiol, A-1180 Vienna, Austria
关键词
PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODIES; CROSS-CLADE NEUTRALIZATION; TO-CHILD TRANSMISSION; IMMUNE-RESPONSES; PASSIVE TRANSFER; ATOMIC-STRUCTURE; SURFACE-ANTIGEN; IN-VITRO; ENVELOPE;
D O I
10.1128/JVI.00184-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.
引用
收藏
页码:5087 / 5100
页数:14
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