Retrovirology

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Reservoir cells no longer detectable after a heterologous SHIV challenge with the synthetic HIV-1 Tat Oyi vaccine

Jennifer D Watkins1, Sophie Lancelot1, Grant R Campbell3, Didier Esquieu2, Jean de Mareuil1, Sandrine Opi4, Sylvie Annappa2, Jean-Pierre Salles2 and Erwann P Loret1*

Author Affiliations

1 UMR Univ. Med./CNRS FRE 2737, Faculté de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille, France

2 SynProsis, Hôtel Technologique BP 100, Technopôle de Château Gombert, 13013 Marseille, France

3 Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0672, USA

4 Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460, USA

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Retrovirology 2006, 3:8 doi:10.1186/1742-4690-3-8

Published: 27 January 2006

Abstract

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.