Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD81 T-cell recall responses

Rapid boosting of memory CD8⁺ T cells (T_M) is essential in cancer immunotherapy and the control of certain infectious diseases. However, effector T cells (T_E) 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 T_E-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 T_E and in close proximity to T_M. The B cells, however, do not serve as APCs in this area. Rather, classic CD⁺ 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.