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K Linde

Publications and source records attributed to K Linde.

At least 37 records · Page 2Linked to original sources
PubMed1983

Stable, highly immunogenic mutants of "Salmonella" with two independent, attenuating markers as potential live vaccine and their validity for "Shigella" and other bacteria.

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.

Animals↗
PubMed1981

[High-immunogenic mutants of Salmonella with two independently of each other attenuating markers as potential vaccines from bacteria capable of multiplication. I. communication: usefulness of the purin-auxotrophy for the isolation of high-immunogenic and stable double-marker strains (author's transl)].

The Salmonella example demonstrates a principle for the isolation of high-immunogenic, stable Salmonella-mutants with two independently of each other attenuating mutations as potential vaccines from bacteria capable of multiplication. The isolation of such double-marker vaccination-strains is verified by the treatment of a single-marker strain (for instance an attenuated high-immunogenic auxotrophic pheno-type) with mutagen and the following selection of clones with the marker purin-auxotrophy as a second attenuating mutation. The demonstrated double-marker strains S. typhimurium his-155 pur-4 and S. dublin met-91 pur-23 are designated by the following parameters: Stability under the conditions of the practical vaccine application; immunogenicity for mice by one immunization only, and separability from homologous wild strains with simple laboratory methods.

Animals↗
PubMed1981

[High-immunogenic mutants of Salmonella with two independently of each other attenuating markers as potential vaccines from bacteria capable of multiplication. 2. Communication: spontaneous chromosomal resistance against antibiotics as a possibility for isolation of clones with decreased virulence (author's transl)].

Mutants of Salmonella typhimurium with spontaneous chromosomal resistance against oleandomycin, streptothricin, nalidixic acid and rifampicin were investigated for their virulence behaviour with the i.p. mouse model. The strains resistant against the special antibiotic consists of a spectrum of various clones with a different behaviour of virulence: Additionally to obvious unchanged virulent strains there are such with a weak or strong attenuation. The majority of the attenuated strains protect the immunized mice against a following lethal wild strain infection. High-immunogenic attenuated double-marker mutants for application as potential vaccine strains may be isolated with the aid of a step by step introduction of a second attenuating "resistance"-marker in a one-marker strain, attenuated for another reason. These strains show the following parameters: -stability under the conditions of practical vaccine application, because a simultaneous back-mutation in both attenuating markers by reason of the unrealizable germ numbers will not occur, -immunogenicity by one immunization only, -separation from homologous wild strains of another origin with simple laboratory methods. This obvious generally acting biological principle is explained on the basis of molecular biological considerations and by referring to the literature. A test for orientation using an attenuated RNA-polymerase mutant showed, the resistance against rifampicin and attenuation are transferred together by co-transduction.

Animals↗
PubMed1980

[Preparation of stable Salmonella vaccine strains through combination of 2 independently attenuating markers with no limitation on growth].

Attenuation by only one single marker with no limitation on propagation (frequency of backmutation being less than 10(-7) will not provide sufficient safety against complications along with vaccination. (This notion, derived from both theoretical considerations and practical experience, does not rule out good stability of certain one-marker mutants under practice conditions.) Two independently attenuating markers with no limitation on propagation, however, do ensure full stability on account of potentiating single frequencies of backmutation (less than 10(-14)). The second attenuating marker must be measurable, and it must not be allowed to bring about substantive reduction in the one-marker mutant's immunogenicity. The following principle was conceptualised for the purpose of resolving the problem: A pool of attenuated highly immunogenic mutants with one single marker without limitation on propagation was rendered available, such as an S-form auxotrophic set of phenotypes (attenuation by co-mutation) or R-form mutants with the potential of tissue persistence. An attenuated second marker then was rendered available which was highly immunogenic as a "one-marker mutant", for example, mutants with adenine (purine) dependence with attenuation a pleiotropic effect and limited availability of metabolities. The second marker was introduced in a one-maker mutant, with verification of additional attenuation along with remaining immunogenicity. The following results were obtained: --Experimental parameters for attenuation and immunogenicity in mice: one single intraperitoneal immunisation, using 10(5), 10(6), 10(7), and 10(8) mutant germs; challenge on 20th day from intraperitoneal immunsation with about 100 LD50; lethality of controls 95 per cent or more; --S. typhimurium his-155/ade-4 and S. dublin met-91/ade-23: LD50: 10(8) germs; Immunogenicity: 90 per cent or more survived exposure to wild strain; --S. cholerae-suis R Dessau/ade-4: LD50: about 10(9) germs; immunogenicity: about 50 per cent only within endotoxic limits, about 10(8) germs or more; --S. typhimurium his-155/marker 2 (enzyme mutation): LD50 about 10(8) germs; immunogenicity: 90 per cent or more survived exposure to wild strain.

Adenine↗
PubMed1978

[Use of attenuated mutants of Pasteurella multocida strain, pathogenic to calves, in experimental mouse model studies. 4. Immunogenicity of selected revertants of temperature-sensitive, streptomycin-dependent mutants as potential vaccine strains].

Temperature-resistant or streptomycin-independent revertants were isolated from temperature-sensitive or streptomycin-dependent mutants of a Pasteurella multocida strain with pathogenicity to calf. The revertants were tested for virulence in mice and for their immunogenicity against wild-strain infection, using 100 times and more of the lethal dose. The following conclusions may be derived from the results thus obtained: 1. Most of the fully attenuated streptomycin-independent revertants failed to provide sufficient protection against wild-strain infection, following one single intraperitoneal immunization. 2. Selected streptomycin-independent revertants protect about 60% of mice immunized with one single intraperitoneal less than or approximately LD10 germ count dose, and 100% of mice immunized two times against lethal challenge. 3. Selected temperature-resistant revertants produced high immunity in mice, with one single intraperitoneally less than or approximately LD10 germ count dose protecting roughly 95 per cent of all animals against lethal infection. 4. The temperature-resistant revertant 9 b/1 and 9 b/5 and the streptomycin-independent revertant 1/14 are on the agenda as potential vaccine strains which can provide full or sufficient protection on the basis of one single immunization.

Animals↗
PubMed1977

The potential of organizations of fee-for-service physicians for achieving significant decreases in hospitalization.

Because hospitalization is a key factor in controlling health care costs and because fee-for-service remains the predominant mode of physician payment, a study was undertaken of the hospitalization experiences of open panel fee-for-service health maintenance organizations (IPA-HMOs) and Foundations for Medical Care (FMCs). Ten open panel plans were surveyed as to characteristics of their programs, physicians, and enrollees and their hospitalization rates. Although data were incomplete, three IPA-HMOs, described as case reports, did achieve striking reductions in hospital use relative to a comparison group or period. Salient characteristics of these plans that may influence hospital use are prepayment by enrollees, sharing by physicians of some financial risk, and effective peer review. Further study is needed, but preliminary indications are that IPA-HMOs have a role to play in reducing health care costs.

Costs and Cost Analysis↗
PubMed1977

[Studies on calf salmonellosis. 3. Preclinical evaluation of a Smd. Salmonella dublin live vaccine].

Results of preclinical assay, preparation and conservation of a S.-dublin live vaccine based on streptomycin dependent mutants and for oral application are demonstrated and discussed in detail. The used oral vaccine is very good tolerated by calves and results in stable immunity after administration of a daily dose of 5 x 10(10) bis 1 x 10(11) living Smd.-mutants for 10 consecutive days. Complete immunity developes in calves within a period of two weeks after the last antigen administration and persists up to the age of 5 to 6 months. Conserving the vaccine at low temperatures (-15 degrees C) the number of living organism is far-reaching preserved in the first 5 months after preparation. After thawing the vaccine is to be used within a period of 3 days. With respect to the preparation of the live vaccine on semisynthetic nutritiv media some informations are given concerning the improvement of bacterial yield.

Administration, Oral↗
PubMed1977

[Studies on calf salmonellosis. 4. Oral and parenteral immunization with live (Smd) and killed antigens].

Reported are results obtained from studies into oral and parenteral immunisation of calf. The approaches had included the use of live (Smd) or dead antigen from Salmonella (S.) dublin and a combination of the two immunisation methods. Live antigen (Smd) was superior to thermally activated dead antigen, when the oral route was used to prevent S.-dublin injection of calves. The above findings were supported by results from analogous studies in which S. typhimurium and S. dublin or live antigen (Smd) or dead antigen, made of the two, had been applied to mice. (One single subcutaneous) parenteral administration did hardly reveal any difference in favour of live vaccine (Smd). Parenteral administration of live or dead antigen proved to be less effective than repeated oral immunisation, particularly when live vaccine (Smd) was used. Immunity not less than up to six months of age against S. dublin wild strain infection can be provided for young calves by oral immunisation, with Smd vaccine (5. 1010 to 1. 1011 live germs/d) being given on ten consecutive days. Calves orally immunised with live antigen (ten repetitive applications of Smd mutants) are likely to develop an antibody titre (H-agglutinins) against S. dublin. Parenteral boostering,using live antigen, has been accompanied by sensitisation due to oral live antigen administration as well as by dose dependence, as was seen from the bactericidal values. Sensitisation was established from orally immunised calves up to three months old (typical booster reaction). Some of it was attributabale to confrontation with wild strains of Salmonella. The H-agglutinin titres of animals aged threemonths in a calf herd with salmonelloses in which all animals had been orally Smd-immunised were close to those recorded from calves in stocks with no salmonellosis occurrence. Under the conditions of oral immunisation, there had obviously been no action of the wild strain which might have triggered intensive antibody formation.

Administration, Oral↗