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Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA<jats:sup>401<\/jats:sup>as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB\/c mice and rhesus macaques, respectively. However, when BCG.HIVA<jats:sup>401<\/jats:sup>was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA<jats:sup>401<\/jats:sup>and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.<\/jats:p>","DOI":"10.1128\/jvi.02607-09","type":"journal-article","created":{"date-parts":[[2010,4,8]],"date-time":"2010-04-08T01:10:20Z","timestamp":1270689020000},"page":"5898-5908","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Novel Recombinant<i>Mycobacterium bovis<\/i>BCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques"],"prefix":"10.1128","volume":"84","author":[{"given":"Maximillian","family":"Rosario","sequence":"first","affiliation":[{"name":"MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Hopkins","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Fulkerson","sequence":"additional","affiliation":[{"name":"Aeras Global TB Vaccine Foundation, 1405 Research Blvd., Rockville, Maryland 20850"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Borthwick","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0301ire F.","family":"Quigley","sequence":"additional","affiliation":[{"name":"Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Joseph","sequence":"additional","affiliation":[{"name":"Catalan HIV Vaccine Research and Development Center, AIDS Research Unit, Infectious Diseases Department, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, School of Medicine, University of Barcelona, 170 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[{"name":"Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui Yee","family":"Greenaway","sequence":"additional","affiliation":[{"name":"Computational Biology Unit, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Venturi","sequence":"additional","affiliation":[{"name":"Computational Biology Unit, Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Gostick","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Price","sequence":"additional","affiliation":[{"name":"Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"},{"name":"Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald W.","family":"Both","sequence":"additional","affiliation":[{"name":"Biotech Equity Partners Pty., Ltd., Riverside Life Sciences Building, 11 Julius Ave., North Ryde, New South Wales 2113, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerald C.","family":"Sadoff","sequence":"additional","affiliation":[{"name":"Aeras Global TB Vaccine Foundation, 1405 Research Blvd., Rockville, Maryland 20850"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toma\u0301s\u030c","family":"Hanke","sequence":"additional","affiliation":[{"name":"MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6290"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0818-9641.2004.01223.x"},{"key":"e_1_3_2_4_2","first-page":"69","volume":"130","year":"2007","unstructured":"Both, G. 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