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


CONCLUSIONS
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.
Watkins
Jennifer D
JD
UMR Univ, Med,/CNRS FRE 2737, Faculté de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille, France. jennifer.watkins@pharmacie.univ-mrs.fr
Lancelot
Sophie
S
Campbell
Grant R
GR
Esquieu
Didier
D
de Mareuil
Jean
J
Opi
Sandrine
S
Annappa
Sylvie
S
Salles
Jean-Pierre
JP
Loret
Erwann P
EP
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization / Q000379:methods; D008253:Macaca mulatta / Q000276:immunology; D011817:Rabbits / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014614:Vaccines, Synthetic; D014765:Viral Vaccines / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015696:Gene Products, tat; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D054322:tat Gene Products, Human Immunodeficiency Virus