rdf:type |
|
lifeskim:mentions |
umls-concept:C0002085,
umls-concept:C0008148,
umls-concept:C0008149,
umls-concept:C0017262,
umls-concept:C0019774,
umls-concept:C0020964,
umls-concept:C0025936,
umls-concept:C0086418,
umls-concept:C0205263,
umls-concept:C0441655,
umls-concept:C0559522,
umls-concept:C1171362,
umls-concept:C1515670,
umls-concept:C1521761
|
pubmed:issue |
12
|
pubmed:dateCreated |
2006-11-22
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pubmed:abstractText |
There is no licensed vaccine available against Chlamydia trachomatis, the leading cause of bacterial sexually transmitted disease. We have found that intranasal immunization with recombinant chlamydial protease-like activity factor (CPAF) induces CD4(+) T-cell- and gamma interferon (IFN-gamma)-dependent protective immunity against murine genital chlamydial infection, thus making CPAF a viable vaccine candidate for further characterization. HLA-DR4 is the predominant allele involved in chlamydial antigen presentation to CD4(+) T cells in humans. We used engineered mice that lack endogenous major histocompatibility complex class II (MHC-II) alleles but express a human HLA allele (HLA-DR4 transgenic [tg] mice) to examine primary immune and CPAF-mediated responses against genital Chlamydia muridarum challenge. Upon primary bacterial exposure, HLA-DR4 tg mice developed Chlamydia-specific IFN-gamma and antibody production and resolved the infection within 30 days, similar to challenged conventional C57BL/6 animals. Moreover, C. muridarum-challenged HLA-DR4 tg mice exhibited CPAF-specific antibody and IFN-gamma production. Upon CPAF-plus-interleukin-12 (IL-12) vaccination, HLA-DR4 tg animals exhibited robust CPAF-specific IFN-gamma production and elevated titers of anti-CPAF total antibody and immunoglobulin G2a (IgG2a) and lower titers of IgG2b and IgG1 antibodies. HLA-DR4 tg and C57BL/6 mice vaccinated with CPAF plus IL-12 resolved the primary genital chlamydial infection significantly earlier than mock-immunized animals, whereas similarly vaccinated MHC class II-deficient mice displayed minimal antigen-specific immune responses and failed to resolve the infection even at 30 days postchallenge. Together, these results demonstrate the importance of human HLA-DR4 molecules in the recognition and presentation of CPAF epitopes, leading to the generation of protective antichlamydial immunity and making these mice a valuable model for mapping HLA-DR4-restricted chlamydial epitopes.
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pubmed:grant |
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-10468609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-10556835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-11083822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-11304554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-11598043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-11739534,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-12010958,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-12710502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-12781697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-1411832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-15213128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-15541719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-15557641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-15688042,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-15905891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-15972540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-16020528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-1691149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-2730867,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-6196835,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-6347323,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-6603741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-7516668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-7591120,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-7642259,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-8676084,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-9328119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-9381524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17015458-9685265
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0019-9567
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
74
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6722-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:17015458-Administration, Intranasal,
pubmed-meshheading:17015458-Alleles,
pubmed-meshheading:17015458-Animals,
pubmed-meshheading:17015458-Antibody Formation,
pubmed-meshheading:17015458-CD4-Positive T-Lymphocytes,
pubmed-meshheading:17015458-Chlamydia Infections,
pubmed-meshheading:17015458-Chlamydia muridarum,
pubmed-meshheading:17015458-Endopeptidases,
pubmed-meshheading:17015458-Female,
pubmed-meshheading:17015458-Genital Diseases, Female,
pubmed-meshheading:17015458-HLA-DR4 Antigen,
pubmed-meshheading:17015458-Humans,
pubmed-meshheading:17015458-Immunoglobulin G,
pubmed-meshheading:17015458-Interferon-gamma,
pubmed-meshheading:17015458-Mice,
pubmed-meshheading:17015458-Mice, Transgenic,
pubmed-meshheading:17015458-Recombinant Proteins,
pubmed-meshheading:17015458-Vaccination
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pubmed:year |
2006
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pubmed:articleTitle |
Chlamydial protease-like activity factor induces protective immunity against genital chlamydial infection in transgenic mice that express the human HLA-DR4 allele.
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pubmed:affiliation |
Department of Biology, University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, TX 78249, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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