1. Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8(+) T-cell recall responses.
- Author
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Zhang L, Bridle BW, Chen L, Pol J, Spaner D, Boudreau JE, Rosen A, Bassett JD, Lichty BD, Bramson JL, and Wan Y
- Subjects
- Acceleration, Animals, B-Lymphocytes metabolism, Cells, Cultured, Gene Transfer Techniques, Immunization, Secondary methods, Mice, Mice, Inbred C57BL, Mice, Transgenic, Vaccination methods, Adenoviridae genetics, B-Lymphocytes transplantation, CD8-Positive T-Lymphocytes immunology, Genetic Vectors administration & dosage, Immunologic Memory genetics, Immunotherapy, Adoptive methods
- 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.
- Published
- 2013
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