title: Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8(+) T-cell recall responses.
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.
authors: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
authors: Liang
authors: L
authors: Zhang
authors: Byram W
authors: BW
authors: Bridle
authors: Lan
authors: L
authors: Chen
authors: Jonathan
authors: J
authors: Pol
authors: David
authors: D
authors: Spaner
authors: Jeanette E
authors: JE
authors: Boudreau
authors: Allison
authors: A
authors: Rosen
authors: Jennifer D
authors: JD
authors: Bassett
authors: Brian D
authors: BD
authors: Lichty
authors: Jonathan L
authors: JL
authors: Bramson
authors: Yonghong
authors: Y
authors: Wan
mesh_terms: D000054:Acceleration; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage*; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory / Q000235:genetics; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014611:Vaccination / Q000379:methods