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Information Technology Solutions TECHNOLOGY CASE 2015 INVENTORS Rick Tarleton Samarchith Karup Chagas Disease Vaccine Demonstrating Enhanced Immunogenicity Background Pathogen-associated molecular patterns, or PAMPs, are molecules associated with groups of pathogens that are recognized by cells of the innate immune system. These molecules can be referred to as small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors and activate innate immune responses which protect the host from infection by identifying conserved non-self molecules. Though PAMPs are known to be fundamental in instigating pathogen-specific immune responses, their role in directing these responses beyond their initiation is less well understood. The persistent pathogen Trypanosoma cruzi, innately deficient in strong PAMPs, presents an ideal template to investigate the impact of temporary or continuous exogenous expression of PAMPs on pathogen control. PATENT INFORMATION Patent Pending CONTACT INFORMATION Rachael Widener, Ph.D. 706-542-5095 [email protected] Homepage: http:// www.ovpr.uga.edu/tco/ Technology Summary UGA researchers have developed a method of using of Toll-like receptor (TLR) ligands—and potentially other PAMPs— as tools to enhance immunogenicity of vaccines, particularly those that might persist for an extended period of time in hosts. More specifically, they have demonstrated that expression of PAMPs by transgenic T. cruzi enhances both innate immune responses and T. cruzi-specific CD8+ T-cell responses. It is thought that the continuous expression of PAMPs by the transgenic parasite is required to sustain the enhanced response and thus promote better control of the infection. Preliminary results of an attenuated Chagas disease vaccine candidate that makes use of PAMPs to enhance immunogenicity are promising. Advantages Increased immunogenicity of vaccine, compared to co-delivery of PAMP or temporary presentation of the beginning of a vaccination regimen, leading to a more protective immune response to the pathogen Demonstrated proof-of-concept using flagellin from Salmonella and porin from Neisseria Pilot study is for Chagas disease, but this methodology could be used to develop vaccines against a variety of pathogens—viral, protozoal, or bacterial Potential Applications Development of a vaccine for Chagas disease Enhance immunogenicity of vaccines, especially those that are against organisms that do not have strong PAMP expression, thereby increasing the efficacy of the vaccine Therapeutic for infection through enhanced host immune response Especially relevant for long-persisting infections Innovative Solutions to Global Needs Information Technology Solutions PRIMARY FOCUS AREAS Vaccines Diagnostics Therapeutics Probiotics Poultry Companion animals Livestock Infectious diseases Wound healing Veterinary Medicine (Continued) Georgia Veterinary Diagnostic Laboratories (www.vet.uga.edu/dlab) The Georgia Veterinary Diagnostic Laboratories provide diagnostic consultation and assistance to practicing veterinarians and animal owners in diagnosing diseases in livestock and pets. A wide range of diagnostic tests are performed daily by the two full-service laboratories in support of veterinarians in Georgia. Faculty of Infectious Diseases (http://fid.uga.edu/) The Faculty of Infectious Diseases effectively addresses infectious disease threats to species and economies world wide by integrating multidisciplinary research in animal, human, and ecosystem health, and by developing successful countermeasures, including vaccines, therapeutics, and diagnostics. LEAD RESEARCHERS Michael Doyle Zhen Fang Fu John Glisson Don Harn Mark Jackwood Larry McDougald Egbert Mundt Fred Quinn Animal Health Research Center Animal Health Research Center allows investigators to study infectious diseases and toxicity problems that plague animal and human populations. Monooclonal Antibody Facility Part of the UGA Animal Care and Use Program, the laboratory functions as a core research laboratory service dedicated to creating custom monoclonal antibodies. Center for Food Safety and Quality Enhancement (CFS) The CFS is associated with the UGA College of Agricultural and Environmental Sciences. CFS faculty conduct research in food safety that benefits the food industry and consumers. Through its programs, CFS has developed strong collaborative ties with the U.S. Centers for Disease Control and Prevention, the USDA Russell Research Center, and other research groups on the Athens campus. Branson Ritchie Steve Stice Ralph Tripp CONTACT INFORMATION Derek E. Eberhart, Ph.D. Phone: 706-542-2207 E-mail: [email protected] Southeastern Cooperative Wildlife Disease Study Provides a variety of diagnostic services throughout a 15-state region. More than 60 species of mammals, birds, reptiles, and amphibians have been studied as part of an internationally recognized research program on wildlife diseases. Center for Molecular BioEngineering (CMBE) Focuses on research for the improvement of biological processes through metabolic engineering. Metabolic engineering involves targeted alteration of biochemical pathways toward the goals of increased yield and productivity of biological products, or for enhanced biodegradation capabilities. Other general objectives of CMBE are to add economic value to underutilized food, agricultural, textile, and paper resources. or Rachael Widener, Ph.D. 706-542-5095 [email protected] Innovative Solutions to Global Needs Information Technology Solutions Live Vaccine to Prevent Enteric Disease TECHNOLOGY CASE 1102 Only recently has the process of energy generation from H2 been recognized as being potentially important for bacterial pathogene- INVENTORS sis within animal hosts (Olson and Maier Robert Maier (2002) Science. 298:788-1790). Hydrogen is John Gunn (The Ohio present in a mammal's digestive tract as a State University) consequence of the fermentive metabolism by the normal colonic flora. Therefore, the possession of hydrogenase enzymes by enteric bacterial strains, together with a readily available source of H2 in the digestive tract, may Background play an important role in enteric bacteria's Enteric pathogens are responsible for an esti- ability to proliferate in the digestive tract. mated 2 million deaths annually and cause PATENT INFORMATION PCT Publication millions more cases of diarrheal illness in hu- Technology Summary mans each year, even in developed countries. Researchers at the University of Georgia and Additionally, enteric diseases are a major The Ohio State University have developed problem in livestock and remain a considera- strains of bacteria that are hydrogenase- ble economic and welfare concern. deficient relative to wild-type strains. WO2005/086669 The engineered bacteria can be used as live attenCausative bacterial agents are transmitted uated vaccines to protect humans and ani- primarily by ingestion of contaminated food, mals against pathogenic enteric bacterial in- CONTACT INFO and although the affected individual typically fections. Rachael Widener, Ph.D. recovers from the abdominal pain and diar- 706-542-5095 [email protected] rhea, they will continue to shed pathogenic bacteria for up to a year after the initial symptoms. Therefore, it is clear the bacteria have http://www.ovpr.uga.edu/ the capability of surviving and growing in the tco/ host. Advantages Easily administered to livestock through drinking water or food Less disruptive method of treating infection than by antibiotics as normal gut flora is not eliminated Based on annotated whole genome sequences, intestinal disease-causing bacteria contain homologous hydrogenases, which are mem- Potential Applications supplements to prevent colonization by brane associated "H2 splitting" enzymes essential for anaerobic metabolism and energy production. Use of live, deficient strains as dietary enteric bacteria in humans and livestock Use of live, deficient strains as vaccines to prevent infection by gut pathogens in humans and livestock Innovative Solutions to Global Needs Information Technology Solutions TECHNOLOGY CASE 1228 Live, Attenuated Rabies Vaccine INVENTORS Dr. Zhen Fang Fu PATENT INFORMATION Patent Pending— PCT (WO 2007/070678) CONTACT INFO Derek E. Eberhart, Ph.D. 706-542-2207 [email protected] Homepage: http:// www.ovpr.uga.edu/tco/ Background Rabies is a viral disease that causes acute and deadly brain inflamma on in mammals. Rabies most o en affects humans in Africa, Asia and South America (~30,000 deaths/year) as well as domes c and wild animals worldwide. Upon infec on, the virus moves through the peripheral nervous system to the central nervous system, a process that takes two to twelve weeks. Once the virus reaches the brain and symptoms have commenced, rabies is almost invariably fatal. Rabies can be prevented in both humans and animals by vaccina on either pre‐exposure or post‐exposure (but before symptom onset). There are several rabies virus vaccines currently on the market, but there is a need for a more effec ve, safe and affordable rabies vaccine. Technology Summary Dr. Zhen Fu of the University of Georgia College of Veterinary Medicine has developed a live a enuated rabies virus that could be useful as a vaccine for both the preven on and treatment of rabies. This vi‐ rus is gene cally modified to express immune factors (cytokines, chemokines, and/or interferons) that enhance its immunogenicity. Its ac va on of the innate, an ‐viral immune response helps to prevent CNS pathology. Advantages Live a enuated vaccine more effec ve in inducing long‐las ng cell‐mediated & humoral immunity Lower dosage and less frequent administra on is required, leading to lower cost; Cheaper vaccines are essen al , as most humans infected with rabies live in the developing world Side effects should be a enuated due to lower vaccine exposure Poten al Applica ons Vaccina on of feral dogs or other wildlife to help prevent human exposure to rabies Vaccina on of companion animals Following further development, possible pre‐exposure prophylaxis for veterinarians, police officers, laboratory workers and others that are at high risk for exposure Post‐exposure treatment of humans Innovative Solutions to Global Needs Information Technology Solutions Poultry Vaccine for Runting Stunting Syndrome TECHNOLOGY CASE 1439 INVENTORS Dr. Egbert Mundt Dr. Holly S. Sellers Dr. Guillermo Zavala Background Runting stunting syndrome (RSS), also known as MAS, infectious stunting syndrome, broiler runting syndrome, pale bird syndrome, and helicopter syndrome, is an economically devastating disease for the poultry industry. The causative agent is unknown, available diagnostic tests are very limited, and there is no vaccine to prevent or mitigate the disease. There is an urgent need for improved reagents, methods and therapeutics for the detection, treatment, and prevention of RSS. Technology Summary PATENT INFORMATION Patent Pending Researchers at the University of Georgia’s Poultry Diagnostic and Research Center identified a unique, viral protein associated with RSS. Using a recombinant version of the protein, they developed an RSS vaccine which provided protection in a newly established RSS challenge model. Offspring of vaccinated breeder hens, subjected to the RSS challenge model, demonstrated a much smaller decrease in weight gain, and dramatically reduced enteropathic cystic lesions in the small intestine, compared to offspring from challenged, nonvaccinated breeders. In addition, an indirect ELISA was established to detect antibodies following vaccination. In summary, this work represents a significant breakthrough in the diagnosis, prevention and treatment of RSS. Advantages CONTACT INFO Derek E. Eberhart, Ph.D. Phone: 706-542-2207 E-mail: [email protected] Homepage: http:// Vaccine for RSS for which no efficacious vaccine is currently available Novel reagents for the detection, treatment, and prevention of RSS Potential Applications www.ovpr.uga.edu/tco/ Diagnosis, treatment and prevention of RSS Innovative Solutions to Global Needs Information Technology Solutions Quick Facts UGA is located in Athens, Georgia, about 60 miles northeast of downtown Atlanta Enrollment in Fall 2008 The University of Georgia Undergraduate 25,303 (UGA), a land-grant and Graduate 8,713 sea-grant state-wide university with commitments Research (FY 2008) and responsibilities, is Income $137.3M Georgia’s flagship institu- Expend. $350.3M tion of higher education. It UGARF $23.75M is also Georgia’s oldest, most diversified institution of higher education and the first state chartered university in the Technology USA. Its motto, “to teach, to serve and to inquire into the nature of things,” reflects the uni- Commercialization versity’s integral and unique role in the conservation and enhancement of the intellectual, Office cultural, and environmental heritage of Georgia and the United States. 8th Floor Boyd GSRC The University of Georgia Research Foundation, Inc. 200 D.W. Brooks Dr. (UGARF) administers all intellectual property developed Athens, GA 30602 at UGA. Working on behalf of UGARF, the Technology USA Commercialization Office (TCO) serves the University of Georgia community by connecting industry with univer- Phone: sity expertise for the public good, promoting economic +1 (706) 542-1404 development, and increasing research visibility. TCO is among the top university technology transfer programs in Fax: the world and is ranked among the top 20 U.S. universi- +1 (706) 542-3837 ties in licensing income (according to the Association of University Technology Transfer Managers). TCO offers a Email: one-stop solution for ease of contracting and industry- [email protected] friendly terms for companies seeking new technologies. Website: w w w. o v p r . u g a . e d u / t c o Advancing the way we live in Georgia and around the globe Information Technology Solutions Advancing the way we live in Georgia and around the globe © The University of Georgia This book contains the descrip on of some technologies developed at The University of Georgia in specific areas, and is not an exhaus ve lis ng of all technologies managed by the University of Georgia Research Founda on, Inc. or of all the scien fic areas represented by our complete por olio of technologies. © The University of Georgia © 2010 University of Georgia Research Foundation, Inc. All rights reserved.