title: Short communication: In vitro synergy between peptides or neutralizing antibodies targeting the N- and C-terminal heptad repeats of HIV Type 1 gp41.
abstract: Class 1 and class 2 fusion peptides bind to the trimeric N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR) regions of HIV-1 envelope glycoprotein gp41, respectively, and block its intramolecular folding required for Env-mediated viral and host cell membrane fusion and subsequent viral entry. Using a combination of T-20 (class 1) and (CCIZN17)(3) (class 2), we provide evidence that these classes of fusion peptides work synergistically in an in vitro infectivity assay in inhibiting the entry of primary HIV-1 isolate 89.6 with combination indexes reaching 0.37 and 0.32 at IC(50) and IC(90), respectively. We further demonstrate a similar degree of neutralization synergy between a monoclonal antibody (MAb), D5, targeting the hydrophobic pocket region of the NHR, and 2F5, a well-characterized MAb that targets the C-terminal end of CHR and the membrane-proximal external region (MPER), providing a rational basis for developing combination vaccines targeting these two highly conserved regions of gp41.
authors.affiliation: Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Hrin
authors.forename: Donna L
authors.initials: DL
authors.lastname: Montgomery
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: Jon H
authors.initials: JH
authors.lastname: Condra
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: An
authors.forename: William R
authors.initials: WR
authors.lastname: Strohl
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bianchi
authors.forename: Antonello
authors.initials: A
authors.lastname: Pessi
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Joyce
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D000077560:Enfuvirtide; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: C504981:(CCIZN17)3 protein; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C514787:gp41 protein, Human immunodeficiency virus 1; D000077560:Enfuvirtide