Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41.

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TitleInduction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41.
Publication TypeJournal Article
Year of Publication2011
AuthorsS Dennison, M, Sutherland, LL, Jaeger, FH, Anasti, KM, Parks, R, Stewart, S, Bowman, C, Xia, S-M, Zhang, R, Shen, X, Scearce, RM, Ofek, GA, Yang, Y, Kwong, PD, Santra, S, Liao, H-X, Tomaras, G, Letvin, NL, Chen, B, S Alam, M, Haynes, BF
JournalPLoS One
Volume6
Issue11
Paginatione27824
Date Published2011
ISSN1932-6203
KeywordsAnimals, Antibody Formation, Antibody Specificity, Cross-Priming, Epitopes, Guinea Pigs, HIV Antibodies, HIV Envelope Protein gp41, HIV-1, Immunization, Liposomes, Macaca mulatta, Neutralization Tests, Peptides, Protein Structure, Quaternary, Recombinant Fusion Proteins
Abstract

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.

DOI10.1371/journal.pone.0027824
Alternate JournalPLoS ONE
PubMed ID22140469
PubMed Central IDPMC3227606
Grant ListAI067854 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States