Enhancing DNA vaccination by sequential injection of lymph nodes with plasmid vectors and peptides |
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Authors: | Kent A Smith Victor L Tam Raymond M Wong Robb R Pagarigan Brenna L Meisenburg Diljeet K Joea Xiping Liu Christiana Sanders David Diamond Thomas M Kündig Zhiyong Qiu Adrian Bot |
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Institution: | 1. Division of Translational Medicine, MannKind Corporation, 28903 North Avenue Paine, Valencia, CA 91355, United States;2. Zürich University Hospital, Zürich, Switzerland |
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Abstract: | DNA vaccines or peptides are capable of inducing specific immunity; however, their translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein, we demonstrate that a novel immunization strategy, encompassing sequential exposure of the lymph node milieu to plasmid and peptide in a heterologous prime-boost fashion, results in considerable MHC class I-restricted immunity in mice. Plasmid-primed antigen expression was essential for the generation of a population of central memory T cells, expressing CD62L and low in PD-1, with substantial capability to expand and differentiate to peripheral memory and effector cells, following subsequent exposure to peptide. These vaccine-induced T cells dominated the T cell repertoire, were able to produce large amounts of chemokines and pro-inflammatory cytokines, and recognized tumor cells effectively. In addition to outlining a feasible and effective method to transform plasmid DNA vaccination into a potentially viable immunotherapeutic approach for cancer, this study sheds light on the mechanism of heterologous prime-boost and the considerable heterogeneity of MHC class I-restricted T cell responses. |
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Keywords: | DNA vaccination Tumor immunity Prime-boost vaccination |
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