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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Enhanced Ex Vivo Stimulation of <italic>Mycobacterium tuberculosis</italic>-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the <italic>Bordetella pertussis</italic> Adenylate Cyclase Vector<xref ref-type="fn" rid="fn3">▿</xref> </title><author><name sortKey="Connell, Tom G" sort="Connell, Tom G" uniqKey="Connell T" first="Tom G." last="Connell">Tom G. Connell</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Shey, Muki S" sort="Shey, Muki S" uniqKey="Shey M" first="Muki S." last="Shey">Muki S. Shey</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Seldon, Ronnett" sort="Seldon, Ronnett" uniqKey="Seldon R" first="Ronnett" last="Seldon">Ronnett Seldon</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Rangaka, Molebogeng X" sort="Rangaka, Molebogeng X" uniqKey="Rangaka M" first="Molebogeng X." last="Rangaka">Molebogeng X. Rangaka</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Van Cutsem, Gilles" sort="Van Cutsem, Gilles" uniqKey="Van Cutsem G" first="Gilles" last="Van Cutsem">Gilles Van Cutsem</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Simsova, Marcela" sort="Simsova, Marcela" uniqKey="Simsova M" first="Marcela" last="Simsova">Marcela Simsova</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Marcekova, Zuzana" sort="Marcekova, Zuzana" uniqKey="Marcekova Z" first="Zuzana" last="Marcekova">Zuzana Marcekova</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Sebo, Peter" sort="Sebo, Peter" uniqKey="Sebo P" first="Peter" last="Sebo">Peter Sebo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Curtis, Nigel" sort="Curtis, Nigel" uniqKey="Curtis N" first="Nigel" last="Curtis">Nigel Curtis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Diwakar, Lavanya" sort="Diwakar, Lavanya" uniqKey="Diwakar L" first="Lavanya" last="Diwakar">Lavanya Diwakar</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Meintjes, Graeme A" sort="Meintjes, Graeme A" uniqKey="Meintjes G" first="Graeme A." last="Meintjes">Graeme A. Meintjes</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Leclerc, Claude" sort="Leclerc, Claude" uniqKey="Leclerc C" first="Claude" last="Leclerc">Claude Leclerc</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wilkinson, Robert J" sort="Wilkinson, Robert J" uniqKey="Wilkinson R" first="Robert J." last="Wilkinson">Robert J. Wilkinson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wilkinson, Katalin A" sort="Wilkinson, Katalin A" uniqKey="Wilkinson K" first="Katalin A." last="Wilkinson">Katalin A. Wilkinson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17522328</idno><idno type="pmc">1951068</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1951068</idno><idno type="RBID">PMC:1951068</idno><idno type="doi">10.1128/CVI.00041-07</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000F72</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F72</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Enhanced Ex Vivo Stimulation of <italic>Mycobacterium tuberculosis</italic>-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the <italic>Bordetella pertussis</italic> Adenylate Cyclase Vector<xref ref-type="fn" rid="fn3">▿</xref> </title><author><name sortKey="Connell, Tom G" sort="Connell, Tom G" uniqKey="Connell T" first="Tom G." last="Connell">Tom G. Connell</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Shey, Muki S" sort="Shey, Muki S" uniqKey="Shey M" first="Muki S." last="Shey">Muki S. Shey</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Seldon, Ronnett" sort="Seldon, Ronnett" uniqKey="Seldon R" first="Ronnett" last="Seldon">Ronnett Seldon</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Rangaka, Molebogeng X" sort="Rangaka, Molebogeng X" uniqKey="Rangaka M" first="Molebogeng X." last="Rangaka">Molebogeng X. Rangaka</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Van Cutsem, Gilles" sort="Van Cutsem, Gilles" uniqKey="Van Cutsem G" first="Gilles" last="Van Cutsem">Gilles Van Cutsem</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Simsova, Marcela" sort="Simsova, Marcela" uniqKey="Simsova M" first="Marcela" last="Simsova">Marcela Simsova</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Marcekova, Zuzana" sort="Marcekova, Zuzana" uniqKey="Marcekova Z" first="Zuzana" last="Marcekova">Zuzana Marcekova</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Sebo, Peter" sort="Sebo, Peter" uniqKey="Sebo P" first="Peter" last="Sebo">Peter Sebo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Curtis, Nigel" sort="Curtis, Nigel" uniqKey="Curtis N" first="Nigel" last="Curtis">Nigel Curtis</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Diwakar, Lavanya" sort="Diwakar, Lavanya" uniqKey="Diwakar L" first="Lavanya" last="Diwakar">Lavanya Diwakar</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Meintjes, Graeme A" sort="Meintjes, Graeme A" uniqKey="Meintjes G" first="Graeme A." last="Meintjes">Graeme A. Meintjes</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Leclerc, Claude" sort="Leclerc, Claude" uniqKey="Leclerc C" first="Claude" last="Leclerc">Claude Leclerc</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wilkinson, Robert J" sort="Wilkinson, Robert J" uniqKey="Wilkinson R" first="Robert J." last="Wilkinson">Robert J. Wilkinson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wilkinson, Katalin A" sort="Wilkinson, Katalin A" uniqKey="Wilkinson K" first="Katalin A." last="Wilkinson">Katalin A. Wilkinson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Clinical and Vaccine Immunology : CVI</title><idno type="ISSN">1556-6811</idno><idno type="eISSN">1556-679X</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The genetically detoxified <italic>Bordetella pertussis</italic> adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay with <italic>Mycobacterium tuberculosis</italic> antigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Clin Vaccine Immunol</journal-id><journal-id journal-id-type="publisher-id">cdli</journal-id><journal-title>Clinical and Vaccine Immunology : CVI</journal-title><issn pub-type="ppub">1556-6811</issn><issn pub-type="epub">1556-679X</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17522328</article-id><article-id pub-id-type="pmc">1951068</article-id><article-id pub-id-type="publisher-id">0041-07</article-id><article-id pub-id-type="doi">10.1128/CVI.00041-07</article-id><article-categories><subj-group subj-group-type="heading"><subject>Microbial Immunology</subject></subj-group></article-categories><title-group><article-title>Enhanced Ex Vivo Stimulation of <italic>Mycobacterium tuberculosis</italic>-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the <italic>Bordetella pertussis</italic> Adenylate Cyclase Vector<xref ref-type="fn" rid="fn3">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Connell</surname><given-names>Tom G.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="fn" rid="fn1">†</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Shey</surname><given-names>Muki S.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Seldon</surname><given-names>Ronnett</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Rangaka</surname><given-names>Molebogeng X.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>van Cutsem</surname><given-names>Gilles</given-names></name><xref ref-type="aff" rid="aff1">3</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Simsova</surname><given-names>Marcela</given-names></name><xref ref-type="aff" rid="aff1">4</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Marcekova</surname><given-names>Zuzana</given-names></name><xref ref-type="aff" rid="aff1">4</xref></contrib><contrib contrib-type="author"><name><surname>Sebo</surname><given-names>Peter</given-names></name><xref ref-type="aff" rid="aff1">4</xref></contrib><contrib contrib-type="author"><name><surname>Curtis</surname><given-names>Nigel</given-names></name><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Diwakar</surname><given-names>Lavanya</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Meintjes</surname><given-names>Graeme A.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Leclerc</surname><given-names>Claude</given-names></name><xref ref-type="aff" rid="aff1">5</xref></contrib><contrib contrib-type="author"><name><surname>Wilkinson</surname><given-names>Robert J.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">6</xref><xref ref-type="fn" rid="fn2">‡</xref></contrib><contrib contrib-type="author"><name><surname>Wilkinson</surname><given-names>Katalin A.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">6</xref><xref ref-type="fn" rid="fn2">‡</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1">Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa,<label>1</label> Department of Paediatrics, University of Melbourne, Infectious Diseases Unit, Department of General Medicine, and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia,<label>2</label> Médecins Sans Frontières, Khayelitsha site B, South Africa,<label>3</label> Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic,<label>4</label> Unite de Régulation Immunitaires et Vaccinologie, Inserm E352, Institut Pasteur, Paris, France,<label>5</label> Wellcome Trust Center for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, United Kingdom<label>6</label></aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Room S2.16, Institute of Infectious Diseases and Molecular Medicine, Wernher & Beit Building South, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, South Africa. Phone: 27 21 406 6793. Fax: 27 21 406 6796. E-mail: <email>katalin.wilkinson@imperial.ac.uk</email></p></fn><fn id="fn1"><label>†</label><p>T.G.C. and M.S.S. are joint first authors.</p></fn><fn id="fn2"><label>‡</label><p>This study was designed by K.A.W., M.X.R., L.D., and R.J.W., with a substantial contribution to conception by G.V.C., M.X.R., G.V.C., L.D., and G.A.M. were responsible for counseling, recruiting, and treating the patients involved. M.S., T.G.C., R.S., L.D., and K.A.W. performed and interpreted the IFNGRAs. T.G.C., K.A.W., R.J.W., and N.C. prepared a draft manuscript that was subsequently approved by all of us.</p></fn></author-notes><pub-date pub-type="ppub"><month>7</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>23</day><month>5</month><year>2007</year></pub-date><volume>14</volume><issue>7</issue><fpage>847</fpage><lpage>854</lpage><history><date date-type="received"><day>24</day><month>12</month><year>2006</year></date><date date-type="rev-recd"><day>27</day><month>3</month><year>2007</year></date><date date-type="accepted"><day>8</day><month>5</month><year>2007</year></date></history><permissions><copyright-statement>Copyright © 2007, American Society for Microbiology</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:href="zcd00707000847.pdf"></self-uri><abstract><p>The genetically detoxified <italic>Bordetella pertussis</italic> adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay with <italic>Mycobacterium tuberculosis</italic> antigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Dose-response curves of HIV-uninfected and HIV-infected persons. (A and B) Responses of six HIV-uninfected and eight HIV-infected persons to CyaA-ESAT-6 (▵), CyaA alone (×), [CyaA-ESAT-6]-CyaA (•), and ESAT-6 (○). Panels C to H represent corrected results, where the response to mock CyaA-E5 is already subtracted (see Materials and Methods). Open circles represent the native TB antigen, black filled circles represent CyaA carrying the antigen inserted at position 336, and black triangles (panels C and D) represent CyaA carrying the antigen inserted at position 224. Data are means ± standards errors.</p></caption><graphic xlink:href="zcd0070730020001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>(A) Whole-blood IFN-γ responses of HIV-infected people with low responses (<250 pg/ml) to the native TB antigen, CyaA-ESAT-6 (<italic>n</italic> = 16), CyaA-CFP-10 (<italic>n</italic> = 14), and CyaA-TB10.3 (<italic>n</italic> = 10). (B) Whole-blood IFN-γ responses of HIV-infected patients with TB with low responses (<250 pg/ml) to the native TB antigen, CyaA-ESAT-6 (<italic>n</italic> = 16), CyaA-CFP-10 (<italic>n</italic> = 13), and CyaA-TB10.3 (<italic>n</italic> = 14). Horizontal bars represent median values.</p></caption><graphic xlink:href="zcd0070730020002"></graphic></fig><table-wrap position="float" id="t1"><label>TABLE 1.</label><caption><p>Criteria for interpretation of the whole-blood IFNGRA for both native antigens and CyaA constructs</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">PHA − nil (pg/ml)<xref ref-type="table-fn" rid="t1fn1"><italic>a</italic></xref></th><th colspan="1" rowspan="1" align="center" valign="bottom">[CyaA-ESAT-6] − [CyaA-E5], [CyaA-CFP-10] − [CyaA-E5], [ESAT-6] − nil, or [CFP-10] − nil (pg/ml)</th><th colspan="1" rowspan="1" align="center" valign="bottom">Result and interpretation</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">≥100</td><td colspan="1" rowspan="1" align="left" valign="top">≥70 and ≥1.5 times WT<xref ref-type="table-fn" rid="t1fn2"><italic>b</italic></xref> or nil</td><td colspan="1" rowspan="1" align="center" valign="top">Positive</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"><100</td><td colspan="1" rowspan="1" align="left" valign="top">≥70 and ≥1.5 times WT or nil</td><td colspan="1" rowspan="1" align="center" valign="top">Positive</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">≥100</td><td colspan="1" rowspan="1" align="left" valign="top"><70</td><td colspan="1" rowspan="1" align="center" valign="top">Negative</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"><100</td><td colspan="1" rowspan="1" align="left" valign="top"><70</td><td colspan="1" rowspan="1" align="center" valign="top">Indeterminate</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">≥100</td><td colspan="1" rowspan="1" align="left" valign="top">≥70 and less than 1.5 times WT or nil</td><td colspan="1" rowspan="1" align="center" valign="top">Indeterminate</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"><100</td><td colspan="1" rowspan="1" align="left" valign="top">≥70 and less than 1.5 times WT or nil</td><td colspan="1" rowspan="1" align="center" valign="top">Indeterminate</td></tr></tbody></table><table-wrap-foot><fn id="t1fn1"><label>a</label><p>The minimum specific activity of the IFN-γ standard used in the assay was 20 U/ng. Therefore, a value recorded as 100 pg/ml is a minimum of 2 U/ml.</p></fn><fn id="t1fn2"><label>b</label><p>WT = background wild-type response (CyaA-E5 alone).</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>TABLE 2.</label><caption><p>IFN-γ results for HIV-uninfected, HIV-infected, and HIV+PTB patients</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Patient group and antigen</th><th colspan="1" rowspan="1" align="center" valign="bottom">IFN-γ (pg/ml)<xref ref-type="table-fn" rid="t2fn1"><italic>a</italic></xref></th><th colspan="1" rowspan="1" align="center" valign="bottom"><italic>P</italic> value<xref ref-type="table-fn" rid="t2fn2"><italic>b</italic></xref></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">HIV<sup>−</sup></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> ESAT-6</td><td colspan="1" rowspan="1" align="center" valign="top">1,510 (0-3,642)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-ESAT-6</td><td colspan="1" rowspan="1" align="center" valign="top">1,388 (176-5,634)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">1,862 (263-5,478)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA/224-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">1,408 (0-7,156)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA/336-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">355 (0-2,450)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Acr2</td><td colspan="1" rowspan="1" align="center" valign="top">460 (0-1,672)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-Acr2</td><td colspan="1" rowspan="1" align="center" valign="top">867 (132-3,060)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> TB10.3</td><td colspan="1" rowspan="1" align="center" valign="top">320 (15-4,011)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-TB10.3</td><td colspan="1" rowspan="1" align="center" valign="top">898 (47-5,450)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">HIV<sup>+</sup></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> ESAT-6</td><td colspan="1" rowspan="1" align="center" valign="top">894 (0-2,685)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.34</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-ESAT-6</td><td colspan="1" rowspan="1" align="center" valign="top">111 (0-1,890)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.02</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">935 (0-2,784)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.13</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA/224-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">463 (0-2,800)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.08</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA/336-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">85 (0-769)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.06</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Acr2</td><td colspan="1" rowspan="1" align="center" valign="top">260 (0-644)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.41</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-Acr2</td><td colspan="1" rowspan="1" align="center" valign="top">200 (0-1,316)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.11</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> TB10.3</td><td colspan="1" rowspan="1" align="center" valign="top">360 (31-1,015)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.56</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-TB10.3</td><td colspan="1" rowspan="1" align="center" valign="top">134 (0-1,692)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.06</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">HIV+PTB</td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> ESAT-6</td><td colspan="1" rowspan="1" align="center" valign="top">377 (0-1,276)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.39</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-ESAT-6</td><td colspan="1" rowspan="1" align="center" valign="top">669 (14-1,790)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.40</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">488 (20-1,599)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.55</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA/224-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">709 (0-1,618)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.87</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA/336-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">174 (0-1,590)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.24</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Acr2</td><td colspan="1" rowspan="1" align="center" valign="top">469 (0-1,296)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.38</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-Acr2</td><td colspan="1" rowspan="1" align="center" valign="top">56 (0-441)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.57</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> TB10.3</td><td colspan="1" rowspan="1" align="center" valign="top">599 (0-1,714)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.71</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> CyaA-TB10.3</td><td colspan="1" rowspan="1" align="center" valign="top">510 (12-2,869)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.58</td></tr></tbody></table><table-wrap-foot><fn id="t2fn1"><label>a</label><p>Values are medians. Values in parentheses are IQRs.</p></fn><fn id="t2fn2"><label>b</label><p><italic>P</italic> values were obtained by comparisons between HIV-uninfected and HIV-infected patients and between HIV-infected and HIV+PTB patients with the Mann-Whitney U test.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t3"><label>TABLE 3.</label><caption><p>Whole-blood IFNGRA results for HIV-infected and HIV-uninfected persons</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="middle">Patient group</th><th colspan="1" rowspan="2" align="center" valign="middle">Antigen (no. of serum samples tested)</th><th colspan="1" rowspan="2" align="center" valign="middle">IFNGRA result</th><th colspan="2" rowspan="1" align="center" valign="bottom">No (%) of serum samples tested with:
<hr></hr></th><th colspan="1" rowspan="2" align="center" valign="middle"><italic>P</italic> value</th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Antigen with CyaA<xref ref-type="table-fn" rid="t3fn2"><italic>b</italic></xref></th><th colspan="1" rowspan="1" align="center" valign="bottom">Antigen alone<xref ref-type="table-fn" rid="t3fn1"><italic>a</italic></xref></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">HIV infected</td><td colspan="1" rowspan="1" align="center" valign="top">ESAT-6 (41)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">18 (44)</td><td colspan="1" rowspan="1" align="center" valign="top">25 (61)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.18</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">14 (34)</td><td colspan="1" rowspan="1" align="center" valign="top">10 (24)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.47</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">9 (22)</td><td colspan="1" rowspan="1" align="center" valign="top">6 (15)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.57</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">CFP-10<xref ref-type="table-fn" rid="t3fn3"><italic>c</italic></xref> (41)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">22 (54)</td><td colspan="1" rowspan="1" align="center" valign="top">26 (63)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.5</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">9 (22)</td><td colspan="1" rowspan="1" align="center" valign="top">8 (20)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">10 (24)</td><td colspan="1" rowspan="1" align="center" valign="top">7 (17)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.59</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">Acr2 (24)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">13 (54)</td><td colspan="1" rowspan="1" align="center" valign="top">14 (58)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">7 (29)</td><td colspan="1" rowspan="1" align="center" valign="top">5 (21)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.74</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">4 (17)</td><td colspan="1" rowspan="1" align="center" valign="top">5 (21)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">TB10.3 (24)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">14 (58)</td><td colspan="1" rowspan="1" align="center" valign="top">17 (71)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.55</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">9 (38)</td><td colspan="1" rowspan="1" align="center" valign="top">4 (17)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.19</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">1 (4)</td><td colspan="1" rowspan="1" align="center" valign="top">3 (12)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.61</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">HIV uninfected</td><td colspan="1" rowspan="1" align="center" valign="top">ESAT-6 (42)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">30 (72)</td><td colspan="1" rowspan="1" align="center" valign="top">28 (67)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.81</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">6 (14)</td><td colspan="1" rowspan="1" align="center" valign="top">8 (19)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.77</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">6 (14)</td><td colspan="1" rowspan="1" align="center" valign="top">6 (14)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">CFP-10 (42)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">28 (67)</td><td colspan="1" rowspan="1" align="center" valign="top">34 (81)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.21</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">9 (21)</td><td colspan="1" rowspan="1" align="center" valign="top">5 (12)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.38</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">5 (12)</td><td colspan="1" rowspan="1" align="center" valign="top">3 (7)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.71</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">Acr2 (35)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">25 (71)</td><td colspan="1" rowspan="1" align="center" valign="top">20 (57)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.32</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">6 (17)</td><td colspan="1" rowspan="1" align="center" valign="top">10 (29)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.4</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">4 (12)</td><td colspan="1" rowspan="1" align="center" valign="top">5 (14)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top">TB10.3 (35)</td><td colspan="1" rowspan="1" align="left" valign="top">Positive</td><td colspan="1" rowspan="1" align="center" valign="top">25 (72)</td><td colspan="1" rowspan="1" align="center" valign="top">23 (66)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.80</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Negative</td><td colspan="1" rowspan="1" align="center" valign="top">5 (14)</td><td colspan="1" rowspan="1" align="center" valign="top">6 (17)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"></td><td colspan="1" rowspan="1" align="center" valign="top"></td><td colspan="1" rowspan="1" align="left" valign="top">Indeterminate</td><td colspan="1" rowspan="1" align="center" valign="top">5 (14)</td><td colspan="1" rowspan="1" align="center" valign="top">6 (17)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td></tr></tbody></table><table-wrap-foot><fn id="t3fn1"><label>a</label><p>The concentrations of antigens used alone were as follows: ESAT-6, 50 nM; CFP-10, 50 nM; Acr2, 50 nM; TB10.3, 5 nM.</p></fn><fn id="t3fn2"><label>b</label><p>The antigens paired with CyaA are termed CyaA-ESAT-6, CyaA-CFP-10, CyaA-Acr2, and CyaA-TB10.3. Each was used at a concentration of 5 nM.</p></fn><fn id="t3fn3"><label>c</label><p>CFP-10 refers to CyaA/224-CFP-10.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t4"><label>TABLE 4.</label><caption><p>Numbers of positive IFNGRA results for HIV-infected and HIV-uninfected persons with presumed LTBI</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="middle">Antigen(s)</th><th colspan="2" rowspan="1" align="center" valign="bottom">No. (%) of positive results
<hr></hr></th><th colspan="1" rowspan="2" align="center" valign="middle"><italic>P</italic> value</th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">HIV<sup>+</sup> (total <italic>n</italic> = 36)<xref ref-type="table-fn" rid="t4fn1"><italic>a</italic></xref></th><th colspan="1" rowspan="1" align="center" valign="bottom">HIV<sup>−</sup> (total <italic>n</italic> = 37)<xref ref-type="table-fn" rid="t4fn1"><italic>a</italic></xref></th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">ESAT-6 and/or CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">25 (69)</td><td colspan="1" rowspan="1" align="center" valign="top">31 (84)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.17</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">CyaA-ESAT-6 and/or CyaA-CFP-10</td><td colspan="1" rowspan="1" align="center" valign="top">20 (56)</td><td colspan="1" rowspan="1" align="center" valign="top">30 (81)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.02</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Any antigens (native and with CyaA)</td><td colspan="1" rowspan="1" align="center" valign="top">31 (86)</td><td colspan="1" rowspan="1" align="center" valign="top">37 (100)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.02</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Tuberculin (by TST)</td><td colspan="1" rowspan="1" align="center" valign="top">20 (55)</td><td colspan="1" rowspan="1" align="center" valign="top">25 (68)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.34</td></tr></tbody></table><table-wrap-foot><fn id="t4fn1"><label>a</label><p>Patients returning for TST reading.</p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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