title: Identification of a highly conserved surface on Tat variants.
abstract: Extracellular Tat is suspected to protect HIV-1-infected cells from cellular immunity. Seropositive patients are unable to produce neutralizing antibodies against Tat, and Tat is still secreted under antiviral treatment. In mice, the Tat OYI vaccine candidate generates neutralizing antibodies such as the mAb 7G12. A peptide called MIMOOX was designed from fragments of Tat OYI identified as the possible binding site for mAb 7G12. MIMOOX was chemically synthesized, and its structure was stabilized with a disulfide bridge. Circular dichroism spectra showed that MIMOOX had mainly β turns but no α helix as Tat OYI. MIMOOX was recognized by mAb 7G12 in ELISA only in reduced conditions. Moreover, a competitive recognition assay with mAb 7G12 between MIMOOX and Tat variants showed that MIMOOX mimics a highly conserved surface in Tat variants. Rat immunizations with MIMOOX induce antibodies recognizing Tat variants from the main HIV-1 subtypes and confirm the Tat OYI vaccine approach.
authors.affiliation: Aix Marseille Université, Unité Mixte de Recherche (UMR) 5236 CNRS, Equipe Technologique de Recherches Appliquées sur le VIH-1 (ETRAV), Faculté de Pharmacie, 27 BD Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mediouni
authors.forename: Albert
authors.initials: A
authors.lastname: Darque
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ravaux
authors.forename: Gilbert
authors.initials: G
authors.lastname: Baillat
authors.forename: Christian
authors.initials: C
authors.lastname: Devaux
authors.forename: Erwann P
authors.initials: EP
authors.lastname: Loret
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D057134:Antibodies, Neutralizing / Q000737:chemistry; D001665:Binding Sites; D001667:Binding, Competitive; D002942:Circular Dichroism; D019295:Computational Biology; D017124:Conserved Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D015497:HIV-1 / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007111:Immunity, Cellular; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: Cellular Immune Response; Epitope Mapping; HIV-1; Protein Design; Tat; Vaccine; Vaccine Development