title: Multi-envelope HIV-1 vaccine devoid of SIV components controls disease in macaques challenged with heterologous pathogenic SHIV.
abstract: A central obstacle to the design of a global HIV-1 vaccine is virus diversity. Pathogen diversity is not unique to HIV-1, and has been successfully conquered in other fields by the creation of vaccine cocktails. Here we describe the testing of an HIV-1 envelope cocktail vaccine. Six macaques received the vaccine, delivered by successive immunizations with recombinant DNA, recombinant vaccinia virus and recombinant envelope proteins. Following vaccination, animals developed a diversity of anti-envelope antibody binding and neutralizing activities toward proteins and viruses that were not represented by sequence in the vaccine. T-cells were also elicited, as measured by gamma-interferon production assays with envelope-derived peptide pools. Vaccinated and control animals were then challenged with the heterologous pathogenic SHIV, 89.6P. Vaccinated monkeys experienced significantly lower virus titers and better maintenance of CD4+ T-cells than unvaccinated controls. The B- and T-cell immune responses were far superior post-challenge in the vaccinated group. Four of six vaccinated animals and only one of six control animals survived a 44-week observation period post-challenge. The present report is the first to describe pathogenic SHIV disease control mediated by a heterologous HIV-1 vaccine, devoid of 89.6 or SIV derivatives.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhan
authors.forename: Louis N
authors.initials: LN
authors.lastname: Martin
authors.forename: Karen S
authors.initials: KS
authors.lastname: Slobod
authors.forename: Chris
authors.initials: C
authors.lastname: Coleclough
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Lockey
authors.forename: Scott A
authors.initials: SA
authors.lastname: Brown
authors.forename: John
authors.initials: J
authors.lastname: Stambas
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sealy
authors.forename: James L
authors.initials: JL
authors.lastname: Blanchard
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
mesh_terms: D016915:AIDS Vaccines / Q000627:therapeutic use*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects*; D008253:Macaca mulatta; D009500:Neutralization Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014611:Vaccination; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines