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We have developed a novel whole-bacterial-cell anthrax vaccine utilizing\n            <jats:italic>B. anthracis<\/jats:italic>\n            that is killed but metabolically active (KBMA). Vaccine strains that are asporogenic and nucleotide excision repair deficient were engineered by deleting the\n            <jats:italic>spoIIE<\/jats:italic>\n            and\n            <jats:italic>uvrAB<\/jats:italic>\n            genes, rendering\n            <jats:italic>B. anthracis<\/jats:italic>\n            extremely sensitive to photochemical inactivation with S-59 psoralen and UV light. We also introduced point mutations into the\n            <jats:italic>lef<\/jats:italic>\n            and\n            <jats:italic>cya<\/jats:italic>\n            genes, which allowed inactive but immunogenic toxins to be produced. Photochemically inactivated vaccine strains maintained a high degree of metabolic activity and secreted protective antigen (PA), lethal factor, and edema factor. KBMA\n            <jats:italic>B. anthracis<\/jats:italic>\n            vaccines were avirulent in mice and induced less injection site inflammation than recombinant PA adsorbed to aluminum hydroxide gel. KBMA\n            <jats:italic>B. anthracis<\/jats:italic>\n            -vaccinated animals produced antibodies against numerous anthrax antigens, including high levels of anti-PA and toxin-neutralizing antibodies. Vaccination with KBMA\n            <jats:italic>B. anthracis<\/jats:italic>\n            fully protected mice against challenge with lethal doses of toxinogenic unencapsulated Sterne 7702 spores and rabbits against challenge with lethal pneumonic doses of fully virulent Ames strain spores. Guinea pigs vaccinated with KBMA\n            <jats:italic>B. anthracis<\/jats:italic>\n            were partially protected against lethal Ames spore challenge, which was comparable to vaccination with the licensed vaccine anthrax vaccine adsorbed. These data demonstrate that KBMA anthrax vaccines are well tolerated and elicit potent protective immune responses. The use of KBMA vaccines may be broadly applicable to bacterial pathogens, especially those for which the correlates of protective immunity are unknown.\n          <\/jats:p>","DOI":"10.1128\/iai.00530-08","type":"journal-article","created":{"date-parts":[[2009,1,24]],"date-time":"2009-01-24T02:41:02Z","timestamp":1232764862000},"page":"1649-1663","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Killed but Metabolically Active\n            <i>Bacillus anthracis<\/i>\n            Vaccines Induce Broad and Protective Immunity against Anthrax"],"prefix":"10.1128","volume":"77","author":[{"given":"Justin","family":"Skoble","sequence":"first","affiliation":[{"name":"Anza Therapeutics Incorporated, Concord, California 94520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Beaber","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Gao","sequence":"additional","affiliation":[{"name":"Cerus Corporation, Concord, California 94520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Lovchik","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie E.","family":"Sower","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqun","family":"Liu","sequence":"additional","affiliation":[{"name":"Anza Therapeutics Incorporated, Concord, California 94520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Luckett","sequence":"additional","affiliation":[{"name":"Anza Therapeutics Incorporated, Concord, California 94520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny W.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Calendar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Portnoy","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, California 94720"},{"name":"School of Public Health, University of California, Berkeley, California 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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