A monoclonal antibody directed against a conformational epitope of the HIV-1 trans-activator (Tat) protein neutralizes cross-clade.
Résumé
The identification of a neutralizing monoclonal antibody (mAb) against extracellular HIV-1 transactivator of transcription (Tat) is important for the development of an efficient HIV-1 treatment. Tat plays an essential role in HIV-1 pathogenesis, not only for HIV-1 replication, but also as an extracellular toxin able to disrupt the immune system. Previously, we showed that immunization of rabbits with Tat Oyi, a variant cloned from an African woman who did not develop AIDS following HIV-1 infection, raised antibodies able to recognize different Tat variants. We carried out mice immunization with Tat Oyi, and selected a mAb, named 7G12, which had the capacity to cross-recognize heterologous Tat variants by a common 3D epitope. These results highlighted that Tat variants were able to acquire a structure, in contrast to a number of studies showing that Tat is as an unfolded protein. MAb 7G12 also had the capacity to neutralize the biological activities of these Tat variants by blocking the cellular uptake of extracellular Tat. This is the first study using Tat Oyi to produce a mAb able to neutralize effectively activities of extracellular Tats from different HIV-1 subtypes. This mAb has an important potential in therapeutic passive immunization and could help HIV-1 infected patients to restore their immunity.