Use of AAV for Immunotherapy

Genetic vaccines are under development for use against diseases where conventional technologies have failed (tuberculosis, HIV and malaria).  They differ from conventional vaccines in that genetic material derived from the pathogen, rather than live or killed forms of the infectious organism, are injected into the host.  Cells that take up this genetic material synthesise proteins normally found in the pathogen and stimulate immunity that can confer protection against the infectious agent.

It is well established that the choice of vector to deliver genetic vaccines has a dominant influence over the character and magnitude of the ensuing immune response.  This project is designed to test the utility of recombinant adeno-associated virus (rAAV) for this purpose, a vector that has the capacity to transduce tissues with high efficiencies and produce long-term expression of vector-encoded transgenes.

We have shown that injection of rAAV encoding malarial antigens into the muscles of mice stimulates immunity specific for the parasite although the magnitude of this response needs to be increased to be effective in controlling infection.  In the course of this investigation, we have also identified a strategy that specifically inhibits immunity.  Although early in its development, it is possible that this strategy might eventually be applied in the clinical setting where specific immune responses need to be circumvented.