Novel Delivery Systems
CVD investigators have tested in adult volunteers a large variety of vaccine adjuvants and vaccine carriers to enhance immunogenicity of numerous subunit microbial vaccines. Examples of experimental adjuvants combined with vaccines and tested in humans are QS-21 saponin and heat labile toxoid of E. coli.
Vaccine antigens have been delivered in clinical trials using biodegradable microspheres and transgenic potatoes, transdermally (dermal hydration and application of an antigen-impregnated patch), as well as in the form of a DNA vaccine encoding hepatitis B surface antigen intradermally.
CVD investigators also have used the zonula occludens toxin (Zot) from Vibrio cholerae for the successful oral delivery of insulin. This native non-cytotoxic protein can reversibly open tight junctions, the structures between gut epithelial cells that affect permeability. Zot is able to alter permeability within 20 minutes, creating a temporary opening for macromolecules to pass through. Oral administration of insulin with Zot to diabetic rats resulted in blood glucose levels comparable to those in rats injected directly with insulin. Current research also involves the use of Zot for delivery of macromolecules across the nasal mucosa and the blood-brain barrier.