NDLI: Paradoxical decrease in the capture and lymph node delivery of cancer vaccine antigen induced by TLR4 agonists as visualized by dual-mode imaging

Content Provider	PubMed Central
Author	Kadayakkara, Deepak K. Korrer, Michael J. Bulte, Jeff W. M. Levitsky, Hyam I.
Abstract	Traditionally, cell-mediated immune responses to vaccination in animal models are evaluated by invasive techniques such as biopsy and organ extraction. We show here that by combining two non-invasive imaging technologies, magnetic resonance imaging (MRI) and bioluminescence imaging (BLI), we can visualize both the afferent and efferent arms of cellular events following vaccination longitudinally. To this end, we evaluated the immune response elicited by a novel toll-like receptor 4 agonist vaccine adjuvant, glucopyranosyl lipid A (GLA), using a whole cell tumor vaccine. Following magnetovaccination, MRI was used to visualize antigen presenting cell-mediated antigen capture and subsequent migration to draining lymph nodes (DLN). Paradoxically, we observed that the incorporation of GLA in the vaccine reduced these critical parameters of the afferent immune response. For the efferent arm, the magnitude of the ensuing antigen-specific T cell response in DLN visualized using BLI correlated with antigen delivery to the DLN as measured by MRI. These findings were confirmed using flow cytometry. In spite of the GLA associated reduction in antigen delivery to the DLN however, the use of GLA as a vaccine adjuvant led to a massive proliferation of vaccine primed antigen-specific T cells in the spleen. This was accompanied by an enhanced tumor therapeutic effect of the vaccine. These findings suggest that GLA adjuvant changes the temporal and anatomical features of both the afferent and efferent arms of the vaccine response and illustrates the utility of quantitative non-invasive imaging as a tool for evaluating these parameters during vaccine optimization.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-14-0820
Ending Page	61
Page Count	11
Starting Page	51
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	1
Volume Number	75
Language	English
Publisher Date	2015-01-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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