Cross-Presentation of Skin-Targeted Recombinant Adenoassociated Virus 2/1 Transgene Induces Potent Resident Memory CD8 ؉ T Cell Responses

A key aspect to consider for vaccinal protection is the induction of a local line of defense consisting of nonrecirculating tissue-resident memory T cells (T RM), in parallel to the generation of systemic memory CD8 ϩ T cell responses. The potential to induce T RM has now been demonstrated for a number of pathogens and viral vectors. This potential, however, has never been tested for recombinant adeno-associated virus (rAAV) vectors, which are weakly inflammatory and poor transducer of dendritic cells. Using a model rAAV2/1-based vaccine, we determined that a single intradermal immunization with rAAV2/1 vectors in mice induces fully functional T RM at the local site of immunization. The optimal differentiation of rAAVinduced transgene-specific skin T RM was dependent on local transgene expression and additional CD4 ϩ T cell help. Transgene expression in dendritic cells, however, appeared to be dispensable for the priming of transgene-specific skin T RM , suggesting that this process solely depends on the cross-presentation of transgene products. Overall, this study provides needed information to properly assess rAAV vectors as T cell-inducing vaccine carriers.