title: Stable, highly immunogenic mutants of "Salmonella" with two independent, attenuating markers as potential live vaccine and their validity for "Shigella" and other bacteria.
abstract: This paper presents for Salmonella sp. an easily realizable principle to develop high-immunogenic, stable live vaccines with two independent attenuating mutations, which is valid for Shigella sp. and Pasteurella s. too. To avoid overattenuation by the stepwise introduction of two attenuating markers, only those mutations are suitable which do not suppress pathogenic structures or essential metabolic functions, but only transduce them into a leaky function, as e.g.: mutagen induced auxotrophic phenotypes with diminished virulence by commutation; purine dependent strains, which hitherto erroneously were regarded as non-immunogenic and particularly distinct chromosomal resistant genotypes, in which the conformational change of the drug target simultaneously causes resistance and changes virulence behaviour (pathwaydrift-mutants). Moreover, in Salmonella, an additional high sensitivity marker against ten sides and drugs possessing a permeation barrier in the outer membrane diminishes--without influence on virulence and immunogenicity--surviving in intestine (bile) and (detergent contaminated) environment. Therefore this hst-marker confers antiepidemic quality to vaccine strains and increases safety. To meet security demands for such vaccines with laboratory methods some easy and practicable tests for standardization are suggested, which include estimation of reversion frequency of pur- and hst marker and the proof of immunogenicity for mice. The safety and efficacy of such vaccine strains are pointed out by veterinarians in live-stock.
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D051379:Mice; D009154:Mutation; D010325:Pasteurella / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D012293:Rifampin / Q000494:pharmacology; D012475:Salmonella / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology / Q000517:prevention & control; D012760:Shigella / Q000235:genetics* / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000276:immunology* / Q000592:standards; D014613:Vaccines, Attenuated
chemical_list: D014612:Vaccines; D014613:Vaccines, Attenuated; D012293:Rifampin