Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses

L Zhang, BW Bridle, L Chen, J Pol… - Blood, The Journal …, 2013 - ashpublications.org
L Zhang, BW Bridle, L Chen, J Pol, D Spaner, JE Boudreau, A Rosen, JD Bassett, BD Lichty
Blood, The Journal of the American Society of Hematology, 2013ashpublications.org
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 …
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.
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