Biomaterial Database

Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1. 1990

A Fontaine, and J Arondel, and P J Sansonetti

Unité de Pathogénie microbienne moléculaire, INSERM U199, Institut Pasteur, Paris.

Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.

UI	MeSH Term	Description	Entries
D008251	Macaca	A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes.	Ape, Barbary,Ape, Black,Ape, Celebes,Barbary Ape,Black Ape,Celebes Ape,Macaque,Apes, Barbary,Apes, Black,Apes, Celebes,Barbary Apes,Black Apes,Celebes Apes,Macacas,Macaques
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001428	Bacterial Vaccines	Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease.	Bacterial Vaccine,Bacterin,Vaccine, Bacterial,Vaccines, Bacterial
D012762	Shigella dysenteriae	A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that is extremely pathogenic and causes severe dysentery. Infection with this organism often leads to ulceration of the intestinal epithelium.	Bacillus dysenteriae,Bacillus dysentericus,Bacillus shigae,Eberthella dysenteriae,Shigella shigae
D012763	Shigella flexneri	A bacterium which is one of the etiologic agents of bacillary dysentery (DYSENTERY, BACILLARY) and sometimes of infantile gastroenteritis.
D014613	Vaccines, Attenuated	Live vaccines prepared from microorganisms which have undergone physical adaptation (e.g., by radiation or temperature conditioning) or serial passage in laboratory animal hosts or infected tissue/cell cultures, in order to produce avirulent mutant strains capable of inducing protective immunity.	Attenuated Vaccine,Vaccines, Live, Attenuated,Attenuated Vaccines,Vaccine, Attenuated
D014614	Vaccines, Synthetic	Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.	Antigens, Synthetic,Chemical Vaccine,Chemical Vaccines,Immunogens, Synthetic,Molecular Vaccine,Molecular Vaccines,Recombinant Vaccine,Semisynthetic Vaccine,Semisynthetic Vaccines,Synthetic Antigen,Synthetic Vaccine,Synthetic Vaccines,Vaccines, Recombinant,Synthetic Antigens,Synthetic Immunogens,Vaccines, Chemical,Vaccines, Molecular,Vaccines, Semisynthetic,Antigen, Synthetic,Recombinant Vaccines,Vaccine, Chemical,Vaccine, Molecular,Vaccine, Recombinant,Vaccine, Semisynthetic,Vaccine, Synthetic
D014774	Virulence	The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.	Pathogenicity