PLOS ONE. 2011; 6(11):e27824.

PubMed ID: 22140469

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

Dennison SM, Sutherland LL, Jaeger FH, Anasti KM, Parks R, Stewart S, Bowman C, Xia SM, Zhang R, Shen X, Scearce RM, Ofek G, Yang Y, Kwong PD, Santra S, Liao HX, Tomaras G, Letvin NL, Chen B, Alam SM, Haynes BF

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.