title: A phase I clinical trial of a multi-epitope polypeptide TAB9 combined with Montanide ISA 720 adjuvant in non-HIV-1 infected human volunteers.
abstract: A phase I clinical trial was performed to examine the safety and immunogenicity of a multi-epitope polypeptide comprising the central 15 amino acids of the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsified in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Three immunisations were given at months 0, 1 and 6 in a randomised, double blind, placebo controlled clinical trial. The placebo was generally well tolerated. However, severe local reactions were observed in TAB9 vaccinated subjects after the second and third inoculations. Seven out of eight volunteers from the lower dose group showed moderate or severe local inflammation, while four out of eight subjects from the higher dose group developed granulomas and sterile abscesses. In general, the reactogenicity depended on the number of inoculations given and the dose of TAB9. Both doses were immunogenic, all immunised volunteers seroconverted and antibodies were broadly reactive against the V3 peptides included in the protein. All vaccine's sera reacted against gp120 in Western blot and 50% of them also neutralised at least one out of five laboratory isolates tested. No differences between doses were found. Anti TAB9 lymphoproliferative responses were observed, being more intense in the high dose group. Due to the strong local reactions that were found in this study, a change in the formulation will be required for further trials with this vaccine candidate in humans.
authors.affiliation: Instituto de Medicina Tropical Pedro Kourí, Autopista Novia del Mediodía. Km 6, La Lisa. Apdo 601, Marianao 13, 11300, Ciudad Habana, Cuba.
authors.forename: H
authors.initials: H
authors.lastname: Toledo
authors.forename: A
authors.initials: A
authors.lastname: Baly
authors.forename: O
authors.initials: O
authors.lastname: Castro
authors.forename: S
authors.initials: S
authors.lastname: Resik
authors.forename: J
authors.initials: J
authors.lastname: Laferté
authors.forename: F
authors.initials: F
authors.lastname: Rolo
authors.forename: L
authors.initials: L
authors.lastname: Navea
authors.forename: L
authors.initials: L
authors.lastname: Lobaina
authors.forename: O
authors.initials: O
authors.lastname: Cruz
authors.forename: J
authors.initials: J
authors.lastname: Míguez
authors.forename: T
authors.initials: T
authors.lastname: Serrano
authors.forename: B
authors.initials: B
authors.lastname: Sierra
authors.forename: L
authors.initials: L
authors.lastname: Pérez
authors.forename: M E
authors.initials: ME
authors.lastname: Ricardo
authors.forename: M
authors.initials: M
authors.lastname: Dubed
authors.forename: A L
authors.initials: AL
authors.lastname: Lubián
authors.forename: M
authors.initials: M
authors.lastname: Blanco
authors.forename: J C
authors.initials: JC
authors.lastname: Millán
authors.forename: A
authors.initials: A
authors.lastname: Ortega
authors.forename: E
authors.initials: E
authors.lastname: Iglesias
authors.forename: E
authors.initials: E
authors.lastname: Pentón
authors.forename: Z
authors.initials: Z
authors.lastname: Martín
authors.forename: J
authors.initials: J
authors.lastname: Pérez
authors.forename: M
authors.initials: M
authors.lastname: Díaz
authors.forename: C A
authors.initials: CA
authors.lastname: Duarte
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000595:Amino Acid Sequence; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008353:Mannitol / Q000008:administration & dosage* / Q000031:analogs & derivatives; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000008:administration & dosage*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000939:Epitopes; D015483:HIV Antibodies; D009829:Oleic Acids; C417682:TAB9; C001681:mannide monooleate; D008353:Mannitol