Controlled Release of NKT Cell Agonist and Non-Replicating Pathogen for Single Dose Vaccination
Abstract
The purpose of this application is to extend the duration of protection after a single vaccination, using novel approaches for controlled release. We hypothesized that targeting a specialized subset of immune cells called NKT-cells will significantly improve the longevity of single-dose non-replicating vaccines which has scope for enhancing immunity against a wide variety of microbial pathogens of concern for military operations. Further improvements in longevity will be achieved via extended release systems. We have formulated vaccines for delivery with or without control release based on particles, for comparing multiple doses with an extended release dose. We have performed two vaccination studies to test the adjuvant effects of different NKT cell activation agents. The first study demonstrated that NKT-cells do indeed enhance immunity against an influenza virus vaccine. The second study was terminated prematurely due to the CoV19 crisis. For the controlled release of vaccine, PLGA microparticles have been synthesized using various types of PLGA. These have been synthesized to encapsulate fluorescein (as a model for alpha-GalCer), gold nanoparticles (as a model for vaccine), and then for alpha-GalCer and H1N1 vaccine. So far, we have achieved an initial release of therapeutic agents followed by minimal passive release. alpha-GalCer release was shown to have an initial burst release followed by minimal diffusional release for 80 days. Release of other molecules, vaccine and alpha-GalCer is still ongoing. The technology being developed should extend current knowledge on using controlled release devices for increasing the durability and longevity of vaccine-induced immunity for influenza. The same controlled-release vaccine concepts should be transferrable to vaccines against other types of human pathogens.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1110052
Entities
People
- John P. Driver
Organizations
- Colorado School of Mines
- University of Florida