Chagas disease vaccine demonstrating enhanced immunogenicity
- *Abstract
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Application
- Vaccine for Chagas disease
- Enhanced immunogenicity, especially againstorganisms that do not have strong PAMP expression, thereby increasing theefficacy of the vaccine
- Therapeutic for infection through enhanced hostimmune response
- Especially relevant for long-persistinginfections
ProblemsAddressed (benefits/advantages)
- Increased immunogenicity of vaccine, comparedto co-delivery of PAMP or temporary presentation of the beginning of avaccination regimen, leading to a more protective immune response to thepathogen
- Demonstrated proof-of-concept using flagellinfrom Salmonella and porin from Neisseria
- Pilot study is for Chagas disease, but thismethodology is a platform that could be used to develop vaccines against avariety of pathogens—viral, protozoal, or bacterial
TechnologySummary
Pathogen-associatedmolecular patterns, or PAMPs, are molecules associated with groups of pathogensthat are recognized by cells of the innate immune system. These molecules can be referred to as smallmolecular motifs conserved within a class of microbes. They are recognized by toll-like receptors(TLRs) and other pattern recognition receptors and activate innate immuneresponses which protect the host from infection by identifying conservednon-self molecules.
ThoughPAMPs are known to be fundamental in instigating pathogen-specific immuneresponses, their role in directing these responses beyond their initiation isless well understood. The persistent pathogen Trypanosoma cruzi, innately deficient in strong PAMPs, presents anideal template to investigate the impact of temporary or continuous exogenousexpression of PAMPs on pathogen control.
UGAresearchers have developed a method of using of Toll-like receptor (TLR)ligands—and potentially other PAMPs— as tools to enhance immunogenicity ofvaccines, particularly those that might persist for an extended period of timein hosts.
Morespecifically, they have demonstrated that expression of PAMPs by transgenic T. cruzi enhances both innate immuneresponses and T. cruzi-specific CD8+T-cell responses. It is thought that thecontinuous expression of PAMPs by the transgenic parasite is required tosustain the enhanced response and thus promote better control of theinfection. Preliminary results of anattenuated Chagas disease vaccine candidate that makes use of PAMPs to enhanceimmunogenicity are promising.
Inventors
RickTarleton,Distinguished Research Professor, Cellular Biology
http://cellbio.uga.edu/directory/faculty/rick-l-tarleton
Researchin the Tarleton laboratory focuses on the immunology and pathogenesis of T. cruzi infection and Chagas disease. Threebroad questions are being addressed: 1) How is immune control initiated andmaintained during the infection; 2) How does T. cruzi manage to avoid immune clearance and maintain an infectionfor decades in hosts; and 3) What is the relationship between immunity,parasite persistence, and disease development? The ultimate goals of these investigations areto provide insights into the immunologic basis of parasite control andpathogenesis in T. cruzi infectionand to use this information to design methods for prevention of infection orintervention in chronic disease.
Samarchith Karup,graduate student
TechnologyDevelopment and IP Status
- Pre-clinicaldevelopment
- PCTpublished: PCT/US2014/011967
- 國家/地區
- 美國
