title: A synthetic HIV-1 Tat protein breaches the skin barrier and elicits Tat-neutralizing antibodies and cellular immunity.
abstract: The HIV-1 Tat protein plays a critical role in the pathogenesis of HIV and has been considered as a candidate vaccine antigen. In an effort to design a non-invasive vaccination strategy against HIV-1 that stimulates the induction of systemic and mucosal immune responses, we studied the transcutaneous delivery of a synthetic Tat protein using cholera toxin as an adjuvant. Following immunization of BALB/c mice with various doses of Tat, IgG and IgA antibody responses were measured in the serum and vaginal washes, respectively. Serum antibodies predominantly recognized the N-terminal and basic functional domains of the protein and exhibited neutralizing capacity against Tat-driven transactivation. Transcutaneous immunization also elicited potent cellular immune responses against Tat and the secretion of high levels of IL-2, IFN-gamma and IL-6. These findings demonstrate for the first time that by using a simple and safe immunization procedure, a synthetic Tat protein can elicit potentially protective immune responses. Transcutaneous immunization may be advantageous for the non-invasive delivery of other HIV candidate vaccine antigens.
authors.affiliation: UPR 9021, Institut de Biologie Moléculaire et Cellulaire, CNRS, Strasbourg, France.
authors.forename: Charalambos D
authors.initials: CD
authors.lastname: Partidos
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Moreau
authors.forename: Olivier
authors.initials: O
authors.lastname: Chaloin
authors.forename: Mélanie
authors.initials: M
authors.lastname: Tunis
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: Claude
authors.initials: C
authors.lastname: Desgranges
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
mesh_terms: D000906:Antibodies / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015696:Gene Products, tat / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D000906:Antibodies; D000939:Epitopes; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus