This work describes targeted mutations applied to several HIV-1 neutralizing antibodies that have been isolated from HIV+ donors. The mutations are designed to increase breadth, potency and half-life to improve potential efficacy for therapeutic application and to decrease immunogenicity to allow for more effective and longer lasting in vivo function. There are also structure-based mutations designed to improve affinity and neutralization potency, which are based on the crystal structures. These modifications are tested against a panel of HIV-1 viruses to determine the breadth and strength of their ability to neutralize. The most potent of these candidates are then selected for testing in in vivo models with the long term goal of testing in humans. In addition, bi-specific antibodies are being developed with the goal of targeting and treating reservoirs of HIV infection in cells.
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|Rudicell, Rebecca S; Kwon, Young Do; Ko, Sung-Youl et al. (2014) Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J Virol 88:12669-82|