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NOVEL ANTI-NEF ANTIBODIES FOR THE DEVELOPMENT OF DRUGS AGAINST HIV-1
The virulence of HIV-1 comes from its substantial replicative capacity and also its pathogenic nature, demonstrated in human and animal models. Several viral gene products contribute directly and indirectly to the pathogenicity and are involved in the development of the acquired immunodeficiency syndrome (AIDS). Among these proteins, Nef constitutes a target of interest as it holds an important role in the viral life cycle. There is no known inhibitor of Nef at this time. In regards to this opportunity, the inventors have developed a new single-domain antibody (sdAB) against the HIV-1 Nef protein The inventors propose the Nef protein as a viral target of major importance for developing inhibitors capable of interfering with its biological functions and, by extension, capable of interfering with the replication and pathogenicity of HIV‑1 and with the immunogenicity of the infected cells. The present invention relates to a novel single-domain antibody fragment (sdAb), with a high affinity (Kd=1.5x10- 10 M), which shows anti-Nef activity in HIV-1 infected cells. When expressed as an intracellular antibody (intrabody) in HIV-1 infected cells, this anti-Nef sdAb is able to inhibit several biological functions of Nef, including the cell-surface CD4 down regulation activity and its positive influence on virus infectivity. Therefore, the designed sdAB appears to be a very good candidate for developing an anti-HIV therapy. BENEFITS The single-domain antibody against Nef protein is of great value and provides the means for developing a promising approach of new therapy against HIV-1. DEVELOPMENT STAGE The anti-Nef sdAb is able to inhibit Nef functions in various HIV-1-infected T lymphocyte cell-lines, such as Jurkat or HPB-ALL CD4-positive T cells. In addition, the anti-Nef sdAb is able to recognize distinct variants of Nef from distinct HIV-1 strains, such as NL43 or SF2 strains.

Technical Description :
The virulence of HIV-1 comes from its substantial replicative capacity and also its pathogenic nature, demonstrated in human and animal models. Several viral gene products contribute directly and indirectly to the pathogenicity and are involved in the development of the acquired immunodeficiency syndrome (AIDS). Among these proteins, Nef constitutes a target of interest as it holds an important role in the viral life cycle. There is no known inhibitor of Nef at this time. In regards to this opportunity, the inventors have developed a new single-domain antibody (sdAB) against the HIV-1 Nef protein The inventors propose the Nef protein as a viral target of major importance for developing inhibitors capable of interfering with its biological functions and, by extension, capable of interfering with the replication and pathogenicity of HIV‑1 and with the immunogenicity of the infected cells. The present invention relates to a novel single-domain antibody fragment (sdAb), with a high affinity (Kd=1.5x10- 10 M), which shows anti-Nef activity in HIV-1 infected cells. When expressed as an intracellular antibody (intrabody) in HIV-1 infected cells, this anti-Nef sdAb is able to inhibit several biological functions of Nef, including the cell-surface CD4 down regulation activity and its positive influence on virus infectivity. Therefore, the designed sdAB appears to be a very good candidate for developing an anti-HIV therapy. BENEFITS The single-domain antibody against Nef protein is of great value and provides the means for developing a promising approach of new therapy against HIV-1. DEVELOPMENT STAGE The anti-Nef sdAb is able to inhibit Nef functions in various HIV-1-infected T lymphocyte cell-lines, such as Jurkat or HPB-ALL CD4-positive T cells. In addition, the anti-Nef sdAb is able to recognize distinct variants of Nef from distinct HIV-1 strains, such as NL43 or SF2 strains.

Potential applications :
Development of new drugs for treatment of HIV-1 infections.

Intellectual property :
Priority patent application FR0708189 entitled: " Fragments danticorps inhibiteurs de la protéine Nef du VIH" filed on November 22,2007 PCT patent application WO2009066241 published on May 28, 2009 Inventors : Daniel BATY, Martine CHARTIER, Patrick CHAMES, Serge Benichou, Stéphane BASMACIOGULLARI, Jérôme BOUCHET

Partnership type :
cnrs-mrs