Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-11-22
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.
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
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0019-9567
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6722-9
pubmed:dateRevised
2009-11-18
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
pubmed:year
2006
pubmed:articleTitle
Chlamydial protease-like activity factor induces protective immunity against genital chlamydial infection in transgenic mice that express the human HLA-DR4 allele.
pubmed:affiliation
Department of Biology, University of Texas at San Antonio, 6900 North Loop 1604 West, San Antonio, TX 78249, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural