title: Fusion-competent vaccines: broad neutralization of primary isolates of HIV.
abstract: Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.
authors.affiliation: The Montana Biotechnology Center and Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: LaCasse
authors.forename: K E
authors.initials: KE
authors.lastname: Follis
authors.forename: M
authors.initials: M
authors.lastname: Trahey
authors.forename: J D
authors.initials: JD
authors.lastname: Scarborough
authors.forename: D R
authors.initials: DR
authors.lastname: Littman
authors.forename: J H
authors.initials: JH
authors.lastname: Nunberg
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D018920:Coculture Techniques; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015726:Giant Cells; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009500:Neutralization Tests; D011487:Protein Conformation; D019713:Receptors, CCR5 / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016915:AIDS Vaccines; D015704:CD4 Antigens; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019713:Receptors, CCR5