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We successfully generated recombinant<jats:italic>Mycobacterium bovis<\/jats:italic>BCG (rBCG) expressing simian immunodeficiency virus (SIV) Gag and Pol as multigenic, nonintegrating vectors, but rBCG-expressing SIV Env was unstable. A dose and route determination study in rhesus monkeys revealed that intramuscular administration of rBCG was associated with local reactogenicity, whereas intravenous and intradermal administration of 10<jats:sup>6<\/jats:sup>to 10<jats:sup>8<\/jats:sup>CFU of rBCG was well tolerated. After single or repeat rBCG inoculations, monkeys developed high-frequency gamma interferon enzyme-linked immunospot responses against BCG purified protein derivative. However, the same animals developed only modest SIV-specific CD8<jats:sup>+<\/jats:sup>T-cell responses. Nevertheless, high-frequency SIV-specific cellular responses were observed in the rBCG-primed monkeys after boosting with recombinant adenovirus 5 (rAd5) expressing the SIV antigens. These cellular responses were of greater magnitude and more persistent than those generated after vaccination with rAd5 alone. The vaccine-elicited cellular responses were predominantly polyfunctional CD8<jats:sup>+<\/jats:sup>T cells. These findings support the further exploration of mycobacteria as priming vaccine vectors.<\/jats:p>","DOI":"10.1128\/jvi.02544-08","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T01:09:14Z","timestamp":1237424954000},"page":"5505-5513","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Recombinant<i>Mycobacterium bovis<\/i>BCG Prime-Recombinant Adenovirus Boost Vaccination in Rhesus Monkeys Elicits Robust Polyfunctional Simian Immunodeficiency Virus-Specific T-Cell Responses"],"prefix":"10.1128","volume":"83","author":[{"given":"Mark J.","family":"Cayabyab","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Korioth-Schmitz","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Carville","sequence":"additional","affiliation":[{"name":"New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harikrishnan","family":"Balachandran","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Miura","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin R.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam P.","family":"Buzby","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barton F.","family":"Haynes","sequence":"additional","affiliation":[{"name":"Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman L.","family":"Letvin","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070784"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12871-12879.2005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-4818"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.11.6622-6632.2004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61591-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.4.1645-1652.2006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11473"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1592"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.08.039"},{"key":"e_1_3_2_11_2","first-page":"471","year":"2009","unstructured":"Douek, D. 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