Recombinant adeno-associated virus (AAV) is now being used in clinical trials as a vector-vaccine against HIV, and is a candidate for use in other vaccines as well. Genes encoded by rAAV are stably expressed for months to years, and the mechanism by which protective immunity is developed to rAAV is yet unknown. In order to address the role of long-term antigen expression on the development of a memory response to rAAV, mice will be used to address the following aims: 1) To define how long-term antigen expression after rAAV vaccination alters the activation, expansion and contraction of antigen-specific CD4+ and CD8+ T cells, 2) To assess whether or not antigen-specific CD8+ T cells primed and maintained in an environment of constant antigen stimulation offer protective immunity in mice, and 3) To examine the relative contribution of variables such as cytokine environment and duration of rAAV-encoded antigen expression on the induction of T cell responses. Results from the experiments proposed in this plan will provide us with a detailed characterization of not only the functional and phenotypic changes associated with CD4+ and CD8+ T cells primed by rAAV, but also their ability to offer in vivo protection from subsequent antigen re-challenge. ? ? ?
| Velazquez, Victoria M; Bowen, David G; Walker, Christopher M (2009) Silencing of T lymphocytes by antigen-driven programmed death in recombinant adeno-associated virus vector-mediated gene therapy. Blood 113:538-45 |
