Research Program TAT

Research Program TAT

The protein « TAT »

The research BIOSANTECH way to fight against the AIDS virus is centered around the protein « Tat » as the target of the vaccine because it is secreted in very early after infection with the virus and the « extra cellular Tat » is suspected to be the cause of the collapse of cellular immunity and maintaining reservoirs virus producing cells.

The « Tat » protein is present in all types and subtypes of HIV-1 present on all continents, its role is extracellular by preventing the removal of the cells by tanks cytoxyques immune system cells (CAMPBELL & LORET 2009 ). It has been shown in clinical trials, there was a correlation between the patients not progress to AIDS and the presence of an immune response against « Tat ». The important question is why only a minority of patients developing an anti-Tat effective, to become non-progressive. It seems that « Tat » has sequence similarities with human proteins in particular, « protamine » (Rodmann and al.1993) which prevents the immune system to defend against the virus during infection.

A study conducted in 1989 on a Gabonese patient cohort exposed to HIV-1 showed that 23 out of 25 infected Gabon, resisted HIV-1 with a variant « Tat » specific to this highly immunogenic region. This strain of HIV-1 specific VHI-called Oyi showed that the only difference with the conventional HIV was a mutation on the gene « Tat ».
Sequencing revealed no abnormality, except gene « Tat » where it was noted a change of Cys 22 Ser. This seems to be the reason for the loss of transactivation (replication and infection) and reversion of this mutation can restore Tat activity (Peloponnese et al. 1999). These atypical patients in the region of Upper Ogooué carriers of this gene « Tat » called « Oyi » were followed for 2 years and remained healthy with no weight loss, no opportunistic disease during the 2 years of the study (Huet & al.1989).
The woman in whom HIV-1 Oyi strain was taken was healthy in 1995 and had three children, all negative (Eric Delaporte, personal communication). The VHI-1 is no longer detectable home.

The research path BIOSANTECH

Biosantech chose to take the license for development and commercialization of the vaccine patents from the « Tat Oyi » which has a mutation of Cys to Ser. Its active ingredient is a synthetic protein to 101 residues long form covered by two patents in 1999 and 2008 by the CNRS and the University of Aix-Marseille. We believe that the « Tat Oyi » give immunity against all variants of HIV-1 present on different continents. The « Tat Oyi » has Epitope 3D corresponding probably to a highly conserved region among different « Tat ». This epitope is present in the 3D « Tat Oyi » but absent in human proteins in particular, « protamine », which would explain the effective anti-Tat response of the holders of this particular strain of HIV-1 virus.

The hypothesis BIOSANTECH

Vaccination of HIV patients, a synthetic active ingredient derived from varying « Tat Oyi » of HIV patients would help the immune system to recognize variants of the protein « Tat » in the blood. Neutralization of the « extra cellular Tat » protein would permit restoration of cellular immunity and elimination of cells infected with HIV-1. The decrease in infected cells should result in the stabilization of viremia in patients without the need for combination therapy. The evidence of efficacy of this vaccine is able to maintain a viremia below 40 copies / ml without using antivirals for two months. This vaccination would be a direct benefit for HIV patients, allowing them to have a normal social life and avoid heavy side effects of combination therapy.

Conclusion

The assumption is that vaccination with an active ingredient synthetically derived variant « Tat Oyi » of HIV-positive patients may help the immune system to recognize variants of the protein « Tat » in the blood. Neutralization of the « extracellular Tat » protein would restore cellular immunity and elimination of cells infected with HIV-1. For vaccinated patients, it could afford to maintain viremia 50 copies / ml without using antivirals. This vaccination would be a direct benefit for HIV patients.