Rapid boosting of memory CD8(+) T cells (TM) is essential in cancer immunotherapy and the control of certain infectious diseases. However, effector T cells (TE) are a barrier to booster vaccination because they can rapidly kill antigen-bearing antigen-presenting cells (APCs) before TM are engaged. We demonstrate that viral-vectored vaccines delivered by B cells elicit robust TM expansion in the presence of TE, enabling booster immunizations to bypass TE-mediated negative feedback regulation. Our data indicate that viral vector-loaded B cells home to the follicular regions in secondary lymphoid organs, which are anatomically separated from TE and in close proximity to TM. The B cells, however, do not serve as APCs in this area. Rather, classic CD11c(+) dendritic cells serve to stimulate the secondary CD8(+) T-cell response. Our data reveal that B cells represent a novel and readily accessible delivery system that can effectively engage secondary CD8(+) T-cell activation for prime-boost strategies.