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

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...

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Veröffentlicht in:	PloS one Jg. 6; H. 11; S. e27824
Hauptverfasser:	Dennison, S. Moses, Sutherland, Laura L., Jaeger, Frederick H., Anasti, Kara M., Parks, Robert, Stewart, Shelley, Bowman, Cindy, Xia, Shi-Mao, Zhang, Ruijun, Shen, Xiaoying, Scearce, Richard M., Ofek, Gilad, Yang, Yongping, Kwong, Peter D., Santra, Sampa, Liao, Hua-Xin, Tomaras, Georgia, Letvin, Norman L., Chen, Bing, Alam, S. Munir, Haynes, Barton F.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States Public Library of Science 30.11.2011 Public Library of Science (PLoS)
Schlagworte:	Animals Antibodies Antibody Formation - immunology Antibody response Antibody Specificity - immunology Antigenic determinants Antigens B cells Binding sites Biology Children & youth Cross-Priming - immunology Deoxyribonucleic acid DNA Epitopes Epitopes - immunology Fusion protein Glycoprotein gp41 Glycoproteins Guinea Pigs HIV HIV Antibodies - blood HIV Antibodies - immunology HIV Envelope Protein gp41 - chemistry HIV Envelope Protein gp41 - immunology HIV-1 - immunology Hospitals Human immunodeficiency virus Immunization Immunoglobulins Infections Infectious diseases Lipids Liposomes Liposomes - chemistry Macaca mulatta - immunology Medicine Neutralization Neutralization Tests Neutralizing Peptides Peptides - chemistry Peptides - immunology Physicians Protein binding Protein Structure, Quaternary Proteins Recombinant Fusion Proteins - metabolism Scaffolds Strategy Well construction Yang, Cindy North Carolina United States > US Maryland Massachusetts
ISSN:	1932-6203, 1932-6203
Online-Zugang:	Volltext
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Zusammenfassung:	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 ⁶⁶⁴DKW 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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: SMD SMA H-XL NLL BFH. Performed the experiments: SMD LLS CB RMS FHJ KMA SS RP S-MX XS RZ SS. Analyzed the data: SMD FHJ KMA RP S-MX GT H-XL SMA BFH. Contributed reagents/materials/analysis tools: YY PDK GO BC. Wrote the paper: SMD SMA BFH.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0027824