title: Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41.
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.
authors.affiliation: Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors.forename: S Moses
authors.initials: SM
authors.lastname: Dennison
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Jaeger
authors.forename: Kara M
authors.initials: KM
authors.lastname: Anasti
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.forename: Shelley
authors.initials: S
authors.lastname: Stewart
authors.forename: Cindy
authors.initials: C
authors.lastname: Bowman
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.forename: Gilad
authors.initials: G
authors.lastname: Ofek
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Georgia
authors.initials: G
authors.lastname: Tomaras
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D008081:Liposomes / Q000737:chemistry; D008253:Macaca mulatta / Q000276:immunology*; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D020836:Protein Structure, Quaternary; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D008081:Liposomes; D010455:Peptides; D011993:Recombinant Fusion Proteins