A major parameter limiting immune responses to vaccination is the number of activated antigen presenting cells (APCs) that capture antigen from the vaccine site and migrate to draining lymph nodes (LNs), the site where T and B cell priming occurs. Currently, a quantitative non-invasive technique for monitoring in vivo antigen capture and dehvery is laclting. The use of cellular magnetic resonance imaging (MRI) is a promising approach for this purpose;however, cellular imaging currently requires ex vivo pre-labeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Using mouse models, we have developed an in vivo labehng method which relies upon the capture of vaccine antigen-associated superparamagnetic iron oxide (SPIO) by endogenous antigen presenting cells, in situ, in order to quantify AFC delivery to LNs. In this system, MRI is capable of monitoring the trafficking of magnetically labeled APCs in vivo that are responsible for inducing tumor-specific immune responses. Analysis of lymph node MR images using dedicated software enables signal quantification through the generation of pixel intensity histograms. Excellent correlation is observed between in vivo and ex vivo quantification of vaccine antigen-loaded APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. Furthermore, APCs that capture SPIO (and antigen) and traffic to LN can subsequently be magnetically recovered ex vivo, allowing for detailed cellular and molecular studies of the upstream parameters that influence the afferent arm of vaccine-induced immunity. Using murine vaccine models targeting lung cancer, we now propose to examine the correlation between the extent of APC trafficking as measured by MRI and the quantity and quality of the downstream immune response. This information will be used to evaluate candidate vaccine adjuvants for their ability to augment this critical step In generating systemic immunity. We will also extend this technology to additional vaccine platforms setting the stage for clinical application.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
United States
Zip Code
Song, Xiaolei; Yang, Xing; Ray Banerjee, Sangeeta et al. (2015) Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen. Contrast Media Mol Imaging 10:74-80
Srivastava, Amit K; Bulte, Jeff W M (2014) Seeing stem cells at work in vivo. Stem Cell Rev 10:127-44
Nimmagadda, Sridhar; Pullambhatla, Mrudula; Lisok, Ala et al. (2014) Imaging Axl expression in pancreatic and prostate cancer xenografts. Biochem Biophys Res Commun 443:635-40
Li, Yang; Foss, Catherine A; Pomper, Martin G et al. (2014) Imaging denatured collagen strands in vivo and ex vivo via photo-triggered hybridization of caged collagen mimetic peptides. J Vis Exp :e51052
Bulte, Jeff W M; Schmieder, Anne H; Keupp, Jochen et al. (2014) MR cholangiography demonstrates unsuspected rapid biliary clearance of nanoparticles in rodents: implications for clinical translation. Nanomedicine 10:1385-8
Bhatnagar, Akrita; Wang, Yuchuan; Mease, Ronnie C et al. (2014) AEG-1 promoter-mediated imaging of prostate cancer. Cancer Res 74:5772-81
Das, Samarjit; Bedja, Djahida; Campbell, Nathaniel et al. (2014) miR-181c regulates the mitochondrial genome, bioenergetics, and propensity for heart failure in vivo. PLoS One 9:e96820
Williford, John-Michael; Wu, Juan; Ren, Yong et al. (2014) Recent advances in nanoparticle-mediated siRNA delivery. Annu Rev Biomed Eng 16:347-70
Shallal, Hassan M; Minn, Il; Banerjee, Sangeeta R et al. (2014) Heterobivalent agents targeting PSMA and integrin-?v?3. Bioconjug Chem 25:393-405
Yang, Xing; Yadav, Nirbhay N; Song, Xiaolei et al. (2014) Tuning phenols with Intra-Molecular bond Shifted HYdrogens (IM-SHY) as diaCEST MRI contrast agents. Chemistry 20:15824-32

Showing the most recent 10 out of 56 publications