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Given the pathogenic potential of<jats:italic>L. monocytogenes<\/jats:italic>, we created an attenuated mutant strain bearing double deletions in the<jats:italic>actA<\/jats:italic>and<jats:italic>plcB<\/jats:italic>virulence genes for an initial clinical safety study of a prototype<jats:italic>L. monocytogenes<\/jats:italic>vector in adults. Twenty healthy volunteers received single escalating oral doses (10<jats:sup>6<\/jats:sup>to 10<jats:sup>9<\/jats:sup>CFU, 4 volunteers per dose cohort) of this attenuated<jats:italic>L. monocytogenes<\/jats:italic>, designated LH1169. Volunteers were monitored in the hospital for 14 days with frequent clinical checks and daily blood and stool cultures, and they were monitored for six additional weeks as outpatients. There were no positive blood cultures and no fevers attributable to the investigational inoculation. Most volunteers shed vaccine bacteria for 4 days or less, without diarrhea. One volunteer had a late positive stool culture during outpatient follow-up. Three volunteers had abnormal liver function test results temporally associated with inoculation; one could be reasonably attributed to another cause. In the highest-dose cohort, humoral, mucosal, and cellular immune responses to the investigational organism were detected in individual volunteers. Attenuated<jats:italic>L. monocytogenes<\/jats:italic>can be studied in adult volunteers without serious long-term health sequelae.<\/jats:p>","DOI":"10.1128\/iai.70.7.3592-3601.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:14Z","timestamp":1027764554000},"page":"3592-3601","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":99,"title":["Safety and Shedding of an Attenuated Strain of<i>Listeria monocytogenes<\/i>with a Deletion of<i>actA\/plcB<\/i>in Adult Volunteers: a Dose Escalation Study of Oral Inoculation"],"prefix":"10.1128","volume":"70","author":[{"given":"Haroula","family":"Angelakopoulos","sequence":"first","affiliation":[{"name":"Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachussetts 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Loock","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachussetts 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Sisul","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachussetts 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric R.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California at Los Angeles School of Medicine, Los Angeles, California 94270"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff F.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California at Los Angeles School of Medicine, Los Angeles, California 94270"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth L.","family":"Hohmann","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Massachusetts General Hospital, Boston, Massachussetts 02114"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.2135-2141.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200004273421702"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.4.3.375-379.1997"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.4.1625-1632.1992"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(95)00027-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/17.2.267"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11890"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.8.3.482-488.2001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(99)80057-6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199701093360204"},{"key":"e_1_3_2_12_2","first-page":"449","volume":"18","year":"2000","unstructured":"DiPetrillo, M. 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