| Abstract: |
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. |
| Keywords: |
genetics; methodology; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; metabolism; animals; mice; cells, cultured; transplantation; mice, inbred c57bl; b lymphocyte; gene transfer; transgenic mouse; c57bl mouse; gene vector; b-lymphocytes; genetic vectors; mice, transgenic; immunology; cell culture; evaluation; vaccination; adoptive immunotherapy; immunotherapy, adoptive; immunologic memory; adenoviridae; gene transfer techniques; immunization; immunization, secondary; immunological memory; adenovirus; acceleration
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