Background: Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine based on a Tat variant of 101 residues called Tat Oyi, which was identified in HIV infected patients in Africa who did not progress to AIDS. We compared, using rabbits, different adjuvants authorized for human use to test on ELISA the recognition of Tat variants from the five main HIV-1 subtypes. A formulation was tested on macaques followed by a SHIV challenge with a European strain.
Results: Tat Oyi with Montanide or Calcium Phosphate gave rabbit sera able to recognize all Tat variants. Five on seven Tat Oyi vaccinated macaques showed a better control of viremia compared to control macaques and an increase of CD8 T cells was observed only on Tat Oyi vaccinated macaques. Reservoir cells were not detectable at 56 days post-challenge in all Tat Oyi vaccinated macaques but not in the controls.
Conclusion: The Tat Oyi vaccine should be efficient worldwide. No toxicity was observed on rabbits and macaques. We show in vivo that antibodies against Tat could restore the cellular immunity and make it possible the elimination of reservoir cells.
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http://dx.doi.org/10.1186/1742-4690-3-8 | DOI Listing |
Retrovirology
May 2016
ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.
Retrovirology
April 2016
ETRAV Laboratory, Faculty of Pharmacy, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.
Background: A Tat Oyi vaccine preparation was administered with informed consent to 48 long-term HIV-1 infected volunteers whose viral loads had been suppressed by antiretroviral therapy (cART). These volunteers were randomized in double-blind method into four groups (n = 12) that were injected intradermally with 0, 11, 33, or 99 µg of synthetic Tat Oyi proteins in buffer without adjuvant at times designated by month 0 (M0), M1 and M2, respectively. The volunteers then underwent a structured treatment interruption between M5 and M7.
View Article and Find Full Text PDFJ Biol Chem
June 2013
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.
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.
View Article and Find Full Text PDFJ Biol Chem
April 2012
Equipe de Recherche Technologique 2011, Université de la Méditerranée, Faculté de Pharmacie, 27 BD Jean Moulin, 13385 Marseille Cedex 5, France.
The identification of a neutralizing mAb against extracellular HIV-1 transactivator of transcription (Tat) is important for the development of an efficient HIV-1 treatment. Tat plays an essential role in HIV-1 pathogenesis, not only for HIV-1 replication but also as an extracellular toxin able to disrupt the immune system. We showed previously that immunization of rabbits with Tat Oyi, a variant cloned from an African woman who did not develop AIDS following HIV-1 infection, raised antibodies able to recognize different Tat variants.
View Article and Find Full Text PDFRetrovirology
January 2006
UMR Univ, Med,/CNRS FRE 2737, Faculté de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille, France.
Background: Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine based on a Tat variant of 101 residues called Tat Oyi, which was identified in HIV infected patients in Africa who did not progress to AIDS. We compared, using rabbits, different adjuvants authorized for human use to test on ELISA the recognition of Tat variants from the five main HIV-1 subtypes.
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