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J Biol Chem. 2013 Jun 28;288(26):19072-80. doi: 10.1074/jbc.M113.466011. Epub 2013 May 15.

Identification of a highly conserved surface on Tat variants.

Author information

1
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.

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.

KEYWORDS:

Cellular Immune Response; Epitope Mapping; HIV-1; Protein Design; Tat; Vaccine; Vaccine Development

PMID:
23678001
PMCID:
PMC3696680
DOI:
10.1074/jbc.M113.466011
[Indexed for MEDLINE]
Free PMC Article
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