Adeno-associated virus delivery of broadly neutralizing antibodies

Abstract

In the present review, we will discuss the emerging field of vector-mediated antibody gene transfer as an alternative HIV vaccine. This approach is an improvement over classical passive immunization strategies that administer antibodies to the host to provide protection from infection. With vector-mediated gene transfer, the antibody gene is delivered to the host, resulting in long-term endogenous antibody expression from the injected muscle that confers protective immunity. Large numbers of very potent and broadly neutralizing HIV antibodies have recently been isolated and characterized. Vector-mediated antibody gene transfer allows one to immediately use these antibodies as a vaccine. Gene transfer studies in both mice and monkeys demonstrate long-term antibody expression in serum from a single injection at concentrations that provide sterilizing immunity. Vector-mediated antibody gene transfer can rapidly move existing, potent anti-HIV molecules into the clinic. The gene transfer products demonstrate a potency and breadth identical to the original product. This strategy eliminates the need for immunogen design and interaction with the adaptive immune system to generate protection, a strategy that so far has shown little promise.