title: Stable Listeria monocytogenes live vaccine candidate strains with graded attenuation on the mouse model.
abstract: Metabolic drift (antibiotics resistance) mutations were used to construct stable two (and three) marker vaccine candidate strains of the predominant Listeria monocytogenes serotypes 1/2a and 4b by stepwise selection. Derived from wild-type strains, spontaneous chromosomal streptomycin-resistant clones with their i.p. LD50 elevated from less than or equal to 10(5.0) c.f.u. to approximately 10(6.1) c.f.u. were used in the second step to isolate the rifampicin-resistant mutants with i.p. LD50 values ranging from 10(6.6) to 10(7.4). On i.p. immunization with fully tolerated doses (less than or equal to 1% LD50), these potential vaccine strains were found to protect not less than 95% of the mice against a lethal (approximately 100 LD50) challenge with the homologous wild-type strain. Further elevation of the i.p. LD50 to greater than 10(8.3) c.f.u. by means of a third attenuating fosfomycin-resistance marker resulted in overattenuation and reduced protective capacity.
authors.affiliation: Institute of Medical Microbiology and Epidemiology, Karl Marx University, Leipzig, GDR.
authors.forename: K
authors.initials: K
authors.lastname: Linde
authors.forename: A A
authors.initials: AA
authors.lastname: Abraham
authors.forename: J
authors.initials: J
authors.lastname: Beer
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000302:isolation & purification*; D004352:Drug Resistance, Microbial / Q000235:genetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000302:isolation & purification; D014774:Virulence / Q000235:genetics
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated