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R Germanier

Publications and source records attributed to R Germanier.

60 records · Page 4Linked to original sources
PubMed1971

Immunity in experimental salmonellosis. II. Basis for the avirulence and protective capacity of gal E mutants of Salmonella typhimurium.

Salmonella typhimurium strains which are deficient in uridine diphosphate (UDP)-galactose-4-epimerase (gal E mutants) owe their outstanding protective capacity when used as live vaccine to the fact that when galactose is supplied exogenously, such as occurs in vivo, smooth cell wall lipopolysaccharides are synthesized. The mutants lose most of their protective capacity when this phenotypic curing is prevented by a second mutation of the kind found in strains LT(2)M(1)A (deficient in galactokinase) or E(32) (deficient in UDP-galactose-lipopolysaccharide transferase). Despite such phenotypic reversion, the gal E mutants are rendered avirulent as a result of galactose-induced bacteriolysis. Secondary mutants have been isolated which differ from each other with respect to the extent of galactose-induced lysis. The differences in galactose sensitivity are attributable to different activities of the other Leoloir pathway enzymes, namely, galactokinase and galactose-1-phosphate-uridyl transferase. The influence of these enzymes on lipopolysaccharide composition and galactose sensitivity and thus on virulence and immunogenicity of gal E mutants has been studied.

Adsorption↗
PubMed1970

Immunity in Experimental Salmonellosis I. Protection Induced by Rough Mutants of Salmonella typhimurium.

Different rough mutants of Salmonella typhimurium were tested to determine their virulence and immunizing capacity when used as live vaccines for mice. All uridine diphosphate-galactose-4-epimeraseless mutants tested were much more potent immunizing agents than any other mutants. This capacity was not correlated with virulence or complexity of cell wall polysaccharide. For good protection, persistence of the rough strains in vivo was essential, but the protection lasted longer than the period during which bacteria were demonstrable in the liver and spleen of the mice. The outstanding immunizing capacity of the "epimeraseless" mutants is not dependent on the persistence of viable bacteria in the mouse.

Journal Article↗
PubMedDate not supplied

Oral vaccination against enteric bacterial infections: an overview.

The present situation and the future prospects for the use of oral vaccines against the major enteric diseases typhoid fever, shigellosis and cholera are discussed in this paper. No significant protection could be demonstrated for oral inactivated whole-cell vaccines. In contrast, an oral live vaccine based on the attenuated Salmonella typhi strain Ty 21a was highly efficacious in volunteer challenge studies and in a controlled field trial. Two attenuated strains are presently being tested in volunteer studies as candidate vaccines against shigellosis; one uses S. typhi Ty 21a and the other Escherichia coli K-12 as the carrier for shigella antigens. Experimental challenge studies in volunteers showed that recovery from clinical cholera confers solid and long-lasting protection. The goal of present research is to develop a vaccine that mimics the events of clinical cholera without causing disease.

Administration, Oral↗
PubMedDate not supplied

Progress in vaccines against typhoid fever.

The widely available heat-phenol-inactivated whole cell typhoid vaccine, which provides approximately 65% protection, has limited usefulness because of the adverse reactions it evokes. In contrast, several new typhoid vaccines promise protection without reactogenicity. Attenuated oral vaccine Ty21a has been evaluated in three field trials of efficacy in Santiago, Chile, involving 530,000 schoolchildren. Three doses of Ty21a in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Fewer doses conferred less protection, while adding a fourth dose significantly enhanced protection; increasing the interval between doses did not improve protection. Large-scale vaccination with Ty21a appeared to cause a herd-immunity effect. Ty21a has reached the stage of being a practical tool for public health. With respect to other vaccines, the safety and immunogenicity of an auxotrophic (Aro-,Pur-) Salmonella typhi mutant (strain 541Ty) has recently been evaluated. Lastly, parenteral purified Vi polysaccharide of S. typhi was safe and immunogenic and provided 64%-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.

Chile↗
PubMedDate not supplied

Use of Pseudomonas aeruginosa toxin A in the construction of conjugate vaccines and immunotoxins.

Pseudomonas aeruginosa toxin A was used to construct conjugate vaccines and potent cytotoxic immunotoxins. Nontoxic, serologically active O polysaccharide derived from P. aeruginosa lipopolysaccharide (LPS) was covalently coupled to toxin A via reductive amination. The conjugate was nontoxic, nonpyrogenic, and had a molecular size of 2 X 10(6). The conjugate vaccine was safe when administered to human volunteers and was capable of evoking an immune response to both LPS and toxin A. Native toxin A was coupled to monoclonal antibodies to the human transferrin receptor and the human interleukin 2 receptor to produce immunotoxins active against receptor-bearing cell lines. Antitumor activity was demonstrated when the immunotoxin directed against the transferrin receptor was administered to nude mice bearing human ovarian tumors.

ADP Ribose Transferases↗