Intranasally administered primary dendritic cell vaccine is capable of inducing a specific T cell response against Coccidioides and PET/CT images and the subsequent biodistribution studies suggested that after intranasal administration of the vaccine, significant number of dendritic cells accumulated in lung, thymus and blood, according to a study published in the Dec. 10 issue in BMC Immunology.
Coccidioidomycosis or valley fever is caused by a highly virulent fungal pathogen: Coccidioides posadasii or immitis and vaccine development against Coccidioides is of contemporary interest because a large number of relapses and clinical failures are reported with antifungal agents.
In the study, Shanjana Awasthi, PhD, assistant professor in the department of pharmaceutical sciences at the University of Oklahoma Health Sciences Center in Oklahoma City, and colleagues have focused on developing a dendritic cell-based vaccine for coccidioidomycosis.
Awasthi and colleagues investigated the immunostimulatory characteristics of an intranasal primary dendritic cell-vaccine in BALB/c mouse strain that is most susceptible to coccidioidomycosis.
The dendritic cells were transfected nonvirally with a plasmid DNA encoding a potent protective epitope of Coccidioides species by Awasthi and colleagues. To enable in vivo monitoring of dendritic cells by PET imaging, the dendritic cells were co-transfected with herpes simplex virus type 1 (HSV1) thymidine kinase cDNA and administered intranasally into mice.
The trafficking and homing of thymidine kinase-expressing dendritic cells were monitored with PET using 18F-labeled 2'- fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodouracil (18F-FIAU) probe.
Based on the PET-probe accumulation in vaccinated mice, selected tissues were studied for antigen-specific response and T cell phenotypes using the enzyme-linked immunosorbent spot (ELISPOT) assay and flow cytometry, respectively.
“In PET images and subsequent biodistribution, intranasally-administered dendritic cells were found to migrate in blood, lung and thymus; lymphocytes showed generation of T effector memory cell population and IFN-gamma release,” according to Awasthi and colleagues.
Awasthi and colleagues noted some technical limitations with 111In-SPECT for dendritic cell -trafficking. One, it does not ensure the integrity of radiolabel and dendritic cell association in vivo, second the resolution is poor, and lastly it allows imaging only up to three to four days. To overcome these limitations, here Awasthi and colleagues used a molecular PET imaging approach. “This is the first time we have been able to study dendritic cell-trafficking in vivo up to seven days of administration," wrote Awasthi and colleagues.
Although the life-span of endogenous dendritic cells is believed to be short, it is not exactly known how long the dendritic cells survive in vivo after administration. “ Our results suggest a likelihood that the primary dendritic cell-based vaccine can circulate in the body for at least seven days of immunization," concluded Awasthi and colleagues.