| Applying TLR synergy in immunotherapy: implications in cutaneous leishmaniasis. | |
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MedLine Citation:
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PMID: 20601594 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Therapy of intracellular pathogens can be complicated by drug toxicity, drug resistance, and the need for prolonged treatment regimens. One approach that has shown promise is immunotherapy. Leishmaniasis, a vector-borne disease ranked among the six most important tropical infectious diseases by the World Health Organization, has been treated clinically with crude or defined vaccine preparations or cytokines, such as IFN-gamma and GM-CSF, in combination with chemotherapy. We have attempted to develop an improved and defined immunotherapeutic using a mouse model of cutaneous leishmaniasis. We hypothesized that immunotherapy may be improved by using TLR synergy to enhance the parasite-specific immune response. We formulated L110f, a well-established Leishmania poly-protein vaccine candidate, in conjunction with either monophosphoryl lipid A, a TLR4 agonist, or CpG, a TLR9 agonist, or a combination of these, and evaluated anti-Leishmania immune responses in absence or presence of active disease. Only mice treated with L110f plus monophosphoryl lipid A-CpG were able to induce a strong effective T cell response during disease and subsequently cured lesions and reduced parasite burden when compared with mice treated with L110f and either single adjuvant. Our data help to define a correlate of protection during active infection and indicate TLR synergy to be a potentially valuable tool in treating intracellular infections. |
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Authors:
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Vanitha S Raman; Ajay Bhatia; Alex Picone; Jacqueline Whittle; Hilton R Bailor; Joanne O'Donnell; Sowmya Pattabhi; Jeffrey A Guderian; Raodoh Mohamath; Malcolm S Duthie; Steven G Reed |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-02 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-09-08 Revised Date: 2011-08-03 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1701-10 Citation Subset: AIM; IM |
Affiliation:
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Infectious Disease Research Institute, Seattle, WA 98104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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administration & dosage Animals Antigens, Bacterial / administration & dosage Bone Marrow Cells / immunology, metabolism Cells, Cultured Cytoskeletal Proteins / physiology Drug Therapy, Combination Female Interleukin-12 / biosynthesis Leishmaniasis, Cutaneous / immunology*, microbiology, therapy* Lipid A / administration & dosage, analogs & derivatives Lipopolysaccharides / administration & dosage Mice Mice, Inbred BALB C Oligodeoxyribonucleotides / administration & dosage Toll-Like Receptors / agonists, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01-AI025038/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Antigens, Bacterial; 0/CPG-oligonucleotide; 0/Cytoskeletal Proteins; 0/Lipid A; 0/Lipopolysaccharides; 0/Oligodeoxyribonucleotides; 0/Toll-Like Receptors; 0/antigen L; 0/marenostrin; 0/monophosphoryl lipid A; 187348-17-0/Interleukin-12 |
| Comments/Corrections | |
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