Title : Impressive virologic suppression of SHIV infection with long-term AAV delivery of monoclonal antibodies
Abstract:
Antibody-based approaches for the treatment or prevention AIDS virus infection are made possible by an incredible array of monoclonal antibodies (mAbs) with potent neutralizing activity against a broad range of HIV isolates. Most infected people do not make such antibodies but we now have them in our possession and they are available for use. While passive administration could be considered, vector delivery using adeno-associated virus (AAV) has a number of distinct advantages. Long-term delivery can be achieved following simple intramuscular administration and AAV has an outstanding safety record in people. These potent broadly neutralizing antibodies are highly divergent from germ line. Consistent with this, we and others have observed a high frequency of antibody responses to such AAV-delivered mAbs that negate continuous delivery. Nonetheless, we now have examples of successful long-term delivery of two such antibodies to each of three SHIV-infected monkeys. Impressive virologic suppression has been observed in all three monkeys for as long as 8 years in the absence of any ART. These findings illustrate the enormous potential for this approach. We have tried a variety of methods for achieving antigen-specific tolerance with this approach without much success. Most recently, we have found one simple, readily applicable approach to allow consistent long-term delivery. The findings will be presented.
