Angelakopoulos, Haroula;
Loock, Katharina;
Sisul, David M.;
Jensen, Eric R.;
Miller, Jeff F.;
Hohmann, Elizabeth L.
Safety and Shedding of an Attenuated Strain ofListeria monocytogeneswith a Deletion ofactA/plcBin Adult Volunteers: a Dose Escalation Study of Oral Inoculation
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Medientyp:
E-Artikel
Titel:
Safety and Shedding of an Attenuated Strain ofListeria monocytogeneswith a Deletion ofactA/plcBin Adult Volunteers: a Dose Escalation Study of Oral Inoculation
Beteiligte:
Angelakopoulos, Haroula;
Loock, Katharina;
Sisul, David M.;
Jensen, Eric R.;
Miller, Jeff F.;
Hohmann, Elizabeth L.
Erschienen:
American Society for Microbiology, 2002
Erschienen in:Infection and Immunity
Sprache:
Englisch
DOI:
10.1128/iai.70.7.3592-3601.2002
ISSN:
0019-9567;
1098-5522
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Listeria monocytogenes</jats:italic>is an intracellular bacterial pathogen which causes bacteremia and has a tropism for the central nervous system and a propensity to cause maternofetal infection.<jats:italic>L. monocytogenes</jats:italic>has been shown to be an effective prophylactic and a therapeutic vaccine vector for viral and tumor antigens in animal models.<jats:italic>L. monocytogenes</jats:italic>mutants lacking the ActA protein, which is essential for intracellular movement, are attenuated but retain immunogenicity in mice. 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>