Abstract
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Objectives Saponin derivatives such as QS-21 have shown remarkable ability as adjuvants (a substance that significantly enhances the immune response to a coadministered antigen) for cancer and infectious disease vaccines. In spite of their widespread use, little is known about the mechanism of immunopotentiation of these saponin adjuvants. Our objective was to radiolabel a unique saponin analog SQS-0-0-5-18 which has demonstrated potent adjuvant activity and study the biodistribution in mice. The information obtained can be helpful in determining which tissues and organs play critical roles in the immunopotentiation by the adjuvants.
Methods [131I]-SQS-0-0-5-18 was labeled by iodination of the corresponding trimethyl tin derivative with [131I]-NaI using chloramine-T as catalyst for 1 min followed by immediate purification using RP-HPLC. In vivo studies were carried out on naive 8-10 week old C57BL/6J female mice. [131I]-SQS-0-0-5-18 (~25 μCi) with 20 μg of cold SQS-0-0-5-18 and 20 μg of ovalbumin was administered s.c and mice were sacrificed 24 h post injection and organs were harvested.
Results Radioiodination was facile with average isolated yields of about 50%. In vivo biodistribution studies indicated that the compound shows high accumulation in the nearest draining lymph nodes with minimal deiodination as measured by activity in the thyroid tissue suggesting a possible mechanism of action. Studies with radioiodinated ovalbumin indicated high deiodination with insignificant accumulation in lymph nodes.
Conclusions We have successfully radiolabeled and studied the biodistribution of a potent immunoadjuvant 0-0-5-18. The high accumulation of the tracer in the lymph nodes potentially indicates that the first step in adjuvant action involves trafficking and/or presentation to the lympocyte rich regions.
Research Support Partial funding for this project was supported by NIH grant 1R01 AI085622-022