Watkins Jennifer D, Lancelot Sophie, Campbell Grant R, Esquieu Didier, de Mareuil Jean, Opi Sandrine, Annappa Sylvie, Salles Jean-Pierre, Loret Erwann P
UMR Univ, Med,/CNRS FRE 2737, Faculté de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille, France.
Retrovirology. 2006 Jan 27;3:8. doi: 10.1186/1742-4690-3-8.
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.
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.
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.
Tat的细胞外作用可能是维持HIV-1感染的CD4 T细胞或储存库细胞的主要原因。我们基于一种名为Tat Oyi的101个氨基酸残基的Tat变体开发了一种合成疫苗，该变体是在非洲未发展为艾滋病的HIV感染患者中鉴定出来的。我们使用兔子比较了不同的人用佐剂，以通过酶联免疫吸附测定（ELISA）测试对五种主要HIV-1亚型的Tat变体的识别。在猕猴身上测试了一种制剂，随后用一种欧洲毒株进行了猿猴-人免疫缺陷病毒（SHIV）攻击。
Tat Oyi与Montanide或磷酸钙联合使用可使兔血清能够识别所有Tat变体。与对照猕猴相比，7只接种Tat Oyi的猕猴中有5只对病毒血症的控制更好，并且仅在接种Tat Oyi的猕猴中观察到CD8 T细胞增加。在所有接种Tat Oyi的猕猴中，攻击后56天未检测到储存库细胞，但在对照中可检测到。
Tat Oyi疫苗在全球范围内应该是有效的。在兔子和猕猴身上未观察到毒性。我们在体内表明，针对Tat的抗体可以恢复细胞免疫，并有可能消除储存库细胞。
