Progress 05/12/05 to 09/30/07
Outputs
OUTPUTS: The important output completed in this work is the potential for enhancing Brucella vaccine efficacy through the use of microencapsulation. Experiments have demonstrate dramatic improvement of protection provided in red deer using currently available vaccine strains in encapsulated format. Oral delivery was shown to provide significant protection from infection and allows vaccination of a greater number of deer or elk than may be achieved using the standard biobullet and does not require additional boosting or animal handling. Dissemination of these results has taken place in the form of presentation at various scientific meetings. These presentations have led to discussions with several companies and potential collaborating scientists. A. M. Arenas*, T. A. Ficht*, M. Kahl*, A. C. Rice-Ficht+ Enhanced Immunogenicity and Protective Efficacy using Live Microencapsulated Vaccines against Brucellosis, Annual Brucellosis Conference, Chicago IL, Dec 2-3, 2006. Arenas-Gamboa, A,
Ficht T, Davis,D, Wong-Gonzalez A, Rice-Ficht A. Enhanced Immune respose of Red Deer (Cervus elaphus) to Live RB51 vaccine strain using Alginate microspheres. CRWAD. Chicago, IL (December 2006) A.M. Arenas, T.A. Ficht, M,M Kahl-McDonagh, A.C. Rice-Ficht. Induction of Protective Immunity Against Brucellosis following Immunization using Live attenuated mutants. Vaccines for Global Health. Galveston, TX (2006) A.M. Arenas, T.A. Ficht, M,M Kahl-McDonagh, A.C. Rice-Ficht. Induction of High Levels of protective Immunity against Brucellosis using Microencapsulation. Bugs, Drugs and Vaccines: securing our future at UTMB (2006) A. M. Arenas, T.A. Ficht, M.M. Kahl-McDonagh, A.C. Rice-Ficht (2006) Development of an Enhanced Immunization System for Brucellosis through Microencapsulation, Presented at the American Society for Microbiology's 106th General Meeting, Orlando, FL, May 2006. Rice-Ficht, A. C., A. G. Arenas, T. A. Ficht, D. S. Davis, P. H. Elzer, K. Nielsen and T. J. Roffe (2005).
Enhanced immune response of Cervus elaphus to live vaccine strains of Brucella abortus through microencapsulation. Proceedings of the American Association of Veterinary Laboratory diagnosticians. 48th Annual Conference. Hershey PA November 5 - 10, 2005, pg. 73.
PARTICIPANTS: Allison Ficht, Professor, Texas A&M Health Science Center Thomas Ficht, Professor College of Veterinary Medicine Don Davis, Assoc. Professor, College of Veterinary Medicine Kristen Nielsen, Graduate Student, Texas A&M Health Science Center Angela Arenas, Graduate Student, DVM, College of Veterinary Medicine Melissa Kahl, Postdoctoral Fellow, College of Veterinary Medicine Alfredo Wong-Gonzalez, Visiting Scientist, University of Monterrey, Mexico The work performed was also supported in part by the United States Geological Survey, National Park Service. The students, postdoctoral fellows and faculty listed above participated in part in the handling and of the animals during various stages of experimentation and took part in sample analysis and data evaluation. Discussion are underway with Alanco, Meriel and INCELL through Nano-Release Technologies to evaluate various candidate vaccines using the encapsulated formats described in this work.
TARGET AUDIENCES: The purpose of these studies was to enhance immune protection against Brucella infection of red deer serving as a model for elk. Transmission from wildlife to cattle posses a serious threat in states were these populations overlap. In that regard the work performed targeted farmers/ranchers whose animals are at risk of exposure. Presentations at meetings including the GYIBC and others were designed to inform individuals of the potential for enhanced immune protection afforded by these approaches.
Impacts
The findings obtained with the Brucella vaccines have encouraged evaluation of encapsulation technology for improved immune protection against additional animal pathogens including fish and swine. This work has provided the foundation for the training of graduate students postdoctoral fellows and DVMs interested in infectious disease research especially those involving large animals. In addition to determining protection against challenge infection, basic studies have revealed significant differences in the host immune response that may explain the enhanced immune protection observed. The results have also led to discussions with Meriel, Alanco (animal health division of Eli Lilly), Pfizer (animal health division), INCELL (San Antonio) and NRT (Nano Release Technologies, College Station, TX) for evaluation with vaccines and encapsulation methods in stimulating the immune response and to provide immune protection against several other agents including several killed and
recombinant products.
Publications
- Angela M. Arenas-Gamboa, Thomas A. Ficht, Don Davis, Alfredo Wong-Gonzalez and Allison Rice-Ficht. 2008. Enhanced Immune Response of Red Deer to live RB51 vaccine strain using alginate microspheres. Accepted in Journal of Wild Life Diseases.
- Angela M Arenas-Gamboa, Thomas. A. Ficht, Melissa, M Kahl-McDonagh, Allison C. Rice-Ficht. 2008. Immunization with a Single Dose of a Microencapsulated Brucella melitensis Mutant Enhances Protection Against Wild-type Challenge. Manuscript submitted to Infection and Immunity.
- Angela M. Arenas-Gamboa, Thomas A. Ficht, Don Davis, Alfredo Wong-Gonzalez and Allison Rice-Ficht. 2008 Vaccination of Cervus elaphus with Brucella abortus vaccine strains through controlled release. Manuscript submitted to Journal of Wild Life Diseases.
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Progress 01/01/06 to 12/31/06
Outputs
Brucellosis is an important zoonotic disease of nearly worldwide distribution. The occurrence of the infection in humans is largely dependent on the prevalence of brucellosis in animal reservoirs, including wildlife. The current vaccine strain used for cattle, RB51 has proven ineffective in protecting bison (Bison bison) and elk (Cervus nelsoni) from infection and abortion. To test possible improvements in vaccine efficacy, a novel approach of immunization was examined using alginate microspheres containing a non-immunogenic eggshell precursor protein of the parasite Fasciola hepatica (vitelline protein B, VpB) to deliver live vaccine RB51 strain. Red deer, (Cervus elaphus) used as a model for elk were vaccinated orally or subcutaneously with 1.5 x1010 viable organisms per animal. Humoral responses post-vaccination (IgG levels) were assessed at different time points and the results indicated that capsules containing live RB51 elicited an anti-Brucella specific IgG
response. Furthermore, animals that received the encapsulated vaccine elicited a cell-mediated response that the nonencapsulated vaccinates failed to produce. Finally, only animals that received encapsulated RB51 vaccine by either route exhibited a significant reduction in bacterial burden in the spleen when challenged with S19 conjunctivally. Together, this data suggests that alginate-VpB microspheres provide a method to enhance the RB51 vaccine performance in elk.
Impacts
The potential to provide protective immunity using an oral delivery system would be ideal for the control of wildlife disease. Brucellosis offers a perfect test vehicle, since the primary cause for concern in this country concerns bison and elk in different parts of the country, but especially in the Greater Yellowstone area. This project employs the use of vaccine strains of demonstrable efficacy in both laboratory and small ruminant systems with a delivery platform that offers a way to enhance safety while simplifying delivery. This is ideal for the control of wildlife-disease that would ordinarily require the roundup and handling of species that are not easily managed.
Publications
- No publications reported this period
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Progress 01/01/05 to 12/31/05
Outputs
In an effort to eliminate or reduce the prevalence of brucellosis in the Greater Yellowstone Area (GYA) using currently licensed vaccine strains and one time delivery, we have undertaken a study of controlled release delivery methods using live encapsulated vaccines. Vaccine strains of Brucella abortus, S19 and RB51, have proven marginally effective in protecting wildlife including bison and elk from infection and abortion. To test possible improvements in vaccine methodology these strains have been microencapsulated and introduced into red deer (Cervus elaphus) to probe alterations of immune response when bacteria are presented in a controlled release format. Bacteria were entrapped in various formulations of protein and alginate microspheres of 400 microns in diameter and introduced as a single dose orally or subcutaneously at 1010 viable organisms per animal. In order to prolong the release of bacteria to the immune system, a special protease-resistant protein
additive (vpB) was incorporated into the formulation. Humoral response to vaccination (serum IgG level) was determined through ELISA at six-week intervals utilizing bacterial lysates of each respective strain as antigen. Groups of nine animals were vaccinated and the titers compared to the titers preceding vaccination. Humoral immunity at six weeks following subcutaneous vaccination with S19 range from 15% to 24% higher than that observed with un-encapsulated S19 and is dependent upon capsule formulation. Titers of animals receiving oral doses of encapsulated S19 range from 50% to 600% compared to control groups but were substantially lower than the subcutaneously injected group. Encapsulated RB51 gave little humoral response at six weeks when injected, but demonstrated a 300% increase in titer over controls at the six-week time point when delivered orally. We predict that the titers of animals receiving capsules that include the vpB additive will show prolonged humoral responses at
later times, as has been observed with mouse vaccination studies. Although data is as yet unavailable demonstrating protection or cell mediated immunity with these specific formulations in cervids, the presence of a humoral response supports the extended release, enhanced delivery and presentation of bacterial antigens to the immune system.
Impacts
The potential to provide protective immunity using an oral delivery system would be ideal for the control of wildlife disease. Brucellosis offers a perfect test vehicle, since the primary cause for concern in this country concerns bison and elk in different parts of the country, but especially in the Greater Yellowstone area. This project employs the use of vaccine strains of demonstrable efficacy in both laboratory and small ruminant systems with a delivery platform that offers a way to enhance safety while simplifying delivery. This is ideal for the control of wildlife-disease that would ordinarily require the roundup and handling of species that are not easily managed.
Publications
- No publications reported this period
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