Paradoxical decrease in the capture and lymph node delivery of cancer vaccine antigen induced by a TLR4 agonist as visualized by dual-mode imaging.
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 noninvasive imaging technologies, 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. After 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 noninvasive imaging as a tool for evaluating these parameters during vaccine optimization.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins School of Medicine, Baltimore, Maryland. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Deepak K
DK
Kadayakkara
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins School of Medicine, Baltimore, Maryland. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Michael J
MJ
Korrer
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins School of Medicine, Baltimore, Maryland. Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Biomedical Engineering, The Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Chemical and Biomolecular Engineering, The Johns Hopkins School of Medicine, Baltimore, Maryland.
Jeff W M
JW
Bulte
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. hy@jhmi.edu.
Hyam I
HI
Levitsky
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064847:Multimodal Imaging / Q000379:methods; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4