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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #322819

Research Project: IDENTIFICATION OF DISEASE MECHANISMS AND DEVELOPMENT OF IMPROVED DIAGNOSTICS AND VACCINES FOR BRUCELLOSIS IN LIVESTOCK AND WILDLIFE

Location: Infectious Bacterial Diseases Research

Title: Live RB51 vaccine lyophilized hydrogel formulations with increased shelf life for practical ballistic delivery

Author
item Falconer, J - University Of Utah
item Christie, R - Colorado State University
item Kaiser, E - Colorado State University
item Olsen, Steven
item Grainger, D - University Of Utah

Submitted to: International Journal of Pharmaceutics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2015
Publication Date: 2/16/2016
Citation: Falconer, J., Christie, R.J., Kaiser, E.J., Olsen, S.C., Grainger, D.W. 2016. Live RB51 vaccine lyophilized hydrogel formulations with increased shelf life for practical ballistic delivery. International Journal of Pharmaceutics. 498(1-2):187-94. doi:10.1016/j.iipharm.2015.12.040.

Interpretive Summary: Brucella abortus is an intracellular pathogen that causes reproductive losses in cattle, bison and elk and which also causes zoonotic infections in people. Regulatory programs in domestic livestock, which include vaccination of livestock, are the most cost-efficient way to control Brucella abortus and prevent human infection. The persistence of brucellosis in bison in Yellowstone National Park may pose a threat for reintroduction of brucelloss to cattle in the United States. In this paper, we evaluated a method to produce a vaccine delivery system which would allow remote vaccination of wildlife against brucellosis. Chemical methods were developed to prepare hydrogels containing the vaccine strain and evaluated for viability, stability, and ability for effective delivery using biodegradable biobullets. This data will be of interest to regulatory personnel, people with responsibilities for management of brucellosis in bison, livestock owners, and other parties with interests regarding brucellosis management.

Technical Abstract: Ballistic delivery capability is essential to delivering vaccines and other therapeutics effectively to both livestock and wildlife in many global scenarios. Here, lyophilized poly(ethylene glycol) (PEG)-glycolide dimethacrylate crosslinked but degradable hydrogels were assessed as payload vehicles to protect and deliver a viable bacterial vaccine, Brucella abortus strain RB51 (RB51), ballistically using commercial thermoplastic cellulosic degradable biobullets. Degradable PEG hydrogel rods loaded with approximately10**10 live RB51 bacteria (CFUs) were fabricated using three different polymerization methods, cut into fixed-sized payload segments, and lyophilized. Resulting dense, glassy RB51 vaccine-loaded monoliths were inserted into thermoplastic biobullet 100-micro L payload chambers. Viability studies of lyophilized formulations assessed as a function of time and storage temperature supported the abilities of several conditions to produce acceptable vaccine shelf-lives. Fired from specifically designed air rifles, gel-loaded biobullets exhibit down-range ballistic properties (i.e., kinetic energy, trajectory, accuracy) similar to unloaded biobullets. Delivered to bovine tissue, these hydrogels rehydrate rapidly by swelling in tissue fluids, with complete hydration observed after 5 hours in serum. Live RB51 vaccine exhibited excellent viability following carrier polymerization, lyophilization, and storage, at levels sufficient for vaccine dosing to wild range bison, the intended target. These data validate lyophilized degradable PEG hydrogel rods as useful drug carriers for remote delivery of both live vaccines and other therapeutics to livestock, wildlife, or other free-range targets using ballistic technologies.