title: Outcome of simian-human immunodeficiency virus strain 89.6p challenge following vaccination of rhesus macaques with human immunodeficiency virus Tat protein.
abstract: The regulatory proteins Nef, Rev, and Tat of human immunodeficiency virus type 1 (HIV-1) are attractive targets for vaccine development, since induction of effective immune responses targeting these early proteins may best control virus replication. Here we investigated whether vaccination with biologically active Tat or inactive Tat toxoid derived from HIV-1(IIIB) and simian-human immunodeficiency virus (SHIV) strain 89.6p would induce protective immunity in rhesus macaques. Vaccination induced high titers of anti-Tat immunoglobulin G in all immunized animals by week 7, but titers were somewhat lower in the 89.6p Tat group. Dominant B-cell epitopes mapped to the amino terminus, the basic domain, and the carboxy-terminal region. Tat-specific T-helper responses were detected in 50% of immunized animals. T-cell epitopes appeared to map within amino acids (aa) 1 to 24 and aa 37 to 66. In addition, Tat-specific gamma interferon responses were detected in CD4+ and/or CD8+ T lymphocytes in 11 of 16 immunized animals on the day of challenge. However, all animals became infected upon intravenous challenge with 30 50% minimal infective doses of SHIV 89.6p, and there were no significant differences in viral loads or CD4+ T-cell counts between immunized and control animals. Thus, vaccination with HIV-1(IIIB) or SHIV 89.6p Tat or with Tat toxoid preparations failed to confer protection against SHIV 89.6p infection despite robust Tat-specific humoral and cellular immune responses in some animals. Given its apparent immunogenicity, Tat may be more effective as a component of a cocktail vaccine in combination with other regulatory and/or structural proteins of HIV-1.
authors.affiliation: Southern Research Institute, Frederick, Maryland. Temple University, Philadelphia, Pennsylvania. Université Pierre et Marie Curie, Paris, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Max W
authors.initials: MW
authors.lastname: Richardson
authors.forename: Jack
authors.initials: J
authors.lastname: Greenhouse
authors.forename: Jake
authors.initials: J
authors.lastname: Yalley-Ogunro
authors.forename: Nigel
authors.initials: N
authors.lastname: Shaw
authors.forename: Jyotika
authors.initials: J
authors.lastname: Mirchandani
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Zagury
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Jay
authors.initials: J
authors.lastname: Rappaport
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D006678:HIV / Q000276:immunology / Q000472:pathogenicity; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015483:HIV Antibodies; C421254:human immunodeficiency virus type 1 Tat vaccine