Abstract
The identification of a neutralizing 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. We showed previously 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 three-dimensional epitope. These results highlighted that Tat variants were able to acquire a structure, in contrast to a number of studies showing Tat 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.
Highlights
Tat, an essential HIV-1 replication factor and extracellular toxin acting on immune cells, is an interesting target to develop therapeutic antibodies
We showed previously 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
MAb 7G12 Cross-recognizes Tat Variants from the Five Main HIV-1 subtypes—Mice were immunized with Tat Oyi, and one IgG1 mAb, named 7G12, was selected among 132 prescreened clones for its broadly reactive immune response against a panel of Tat variants representative of main HIV-1 clades (Fig. 1)
Summary
An essential HIV-1 replication factor and extracellular toxin acting on immune cells, is an interesting target to develop therapeutic antibodies. We showed previously 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 three-dimensional epitope These results highlighted that Tat variants were able to acquire a structure, in contrast to a number of studies showing Tat as an unfolded protein. 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. We selected one IgG1 mAb, named 7G12, showing an efficient cross-recognition against various HIV-1 subtypes. mAb 7G12 was able to neutral-
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