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Biomedical subjects

K Linde

Publications and source records attributed to K Linde.

At least 19 recordsLinked to original sources
PubMed1995

The efficacy of a live Listeria monocytogenes combined serotype 1/2a and serotype 4b vaccine.

In each of two experiments, sheep and lambs were vaccinated by a subcutaneous injection of a test vaccine (consisting of a combined serotype 1/2a and serotype 4b live Listeria monocytogenes culture) and challenged 16 days later with a mixture of the homologous wild strains. After challenge, the mortality rate of vaccinated sheep was 28.1% and that of controls 71.9%; that of lambs was 25.0%, although these had been inoculated with the LD70 dose. Furthermore, in each of two field trials in Listeria-infected flocks, primiparous pregnant ewes were vaccinated. In the first field trial, 3 or 110 lambs died of listeriosis of those born of vaccinated (n = 564) or unvaccinated (n = 3345) ewes, respectively. In the second, the perinatal mortality rate of lambs born of vaccinated or unvaccinated ewes was 7.6 or 30.3%, respectively, and the mean birth weight of lambs born of vaccinated or control ewes was 2.2 or 1.8 kg, respectively; the mean milk production of vaccinated ewes was 106 and that of controls 83 l; no Listeria was isolated from milk samples of vaccinated ewes. It is concluded that the vaccine is efficacious for the protection of sheep from listeriosis.

Animals↗
PubMed1992

Prophylaxis of Salmonella abortus ovis-induced abortion of sheep by a Salmonella typhimurium live vaccine.

A Salmonella typhimurium live vaccine with optimal level of attenuation for sheep, constructed by means of 'metabolic drift' mutations, was tested for its efficacy in preventing Salmonella abortus ovis-induced abortions. In two field trials in Kirgiziya, 78,000 to 100,000 first delivery sheep received a fully tolerated single dose of 10(9) c.f.u. live vaccine 2 months before to 4 months after insemination. Alternatively, they were immunized twice with commercial inactivated S. abortus ovis vaccine, or they served as non-immunized controls. The S. abortus ovis-induced abortion frequency in the controls was greater than or equal to 30%, in sheep immunized with inactivated vaccine greater than or equal to 11%. In flocks immunized with live vaccine, the S. abortus ovis-induced abortion frequency did not exceed 0.1%. Thus, use of 'metabolic drift' mutations for construction of stable vaccine strains optimally attenuated for the particular host species proved to be relevant to practice.

Abortion, Veterinary↗
PubMed1992

Humoral and cell-mediated immunity in mice after immunization with live oral vaccines of Salmonella typhimurium: auxotrophic mutants with two attenuating markers.

Persistence and clearance of the vaccinal strains, humoral and cell-mediated immune response and protective immunity were assessed in ICR mice, immunized intraperitoneally or intragastrically with double-marker auxotrophic mutants of Salmonella typhimurium strains 1771 and 3334 (his-pur-). Strain 3334 possesses in addition the antiepidemic Hst (high sensitivity to tensides) marker which confers decreased survival in the gut and environment. The results showed that the strains are not overattenuated. They revealed preserved multiplication capacity, established carrier state for 28-30 days and induced humoral and cell-mediated immunity as measured by passive haemolysis and microagglutination or footpad swelling tests, respectively. The immune response was determined by biological features of the strains. Strain 1771 induced synthesis of O- and H-antibodies 7-11 days earlier than strain 3334. Footpad reactions appeared 3-4 days after immunization and a week before the serum antibodies. Cell-mediated immunity showed clear correlation with the protection against challenge with a virulent strain. The present results suggest that the double-marker auxotrophic mutants of S. typhimurium might prove very useful in the development of a live vaccine in further studies on livestock.

Administration, Oral↗
PubMed1992

Testosterone increases serum 1,25-dihydroxyvitamin D and insulin-like growth factor-I in hypogonadal men.

The short-term metabolic effects of testosterone treatment on circulating levels of 1,25-dihydroxyvitamin D and insulin-like growth factor-I (IGF-I) were studied in 13 hypogonadal men. The study group included 11 men with Klinefelter's syndrome, with varying degree of androgen deficiency, and two men with secondary hypogonadism. Pretreatment levels of 1,25-dihydroxyvitamin D, vitamin D-binding protein and IGF-binding protein-I were all within the normal range. The levels of IGF-I were lower than normal in 5/11 of the Klinefelter patients and in one patient with GH-deficiency. Testosterone treatment increased circulating total 1,25-dihydroxyvitamin D significantly from 75 +/- 4 pmol l-1 (mean +/- SEM) to 86 +/- 4 (P less than 0.01) and the free 1,25-dihydroxyvitamin D-index from 1.95 +/- 0.11 to 2.39 +/- 0.12 (P less than 0.01). Serum levels of IGF-I increased from 117 +/- 22 micrograms/l to 143 +/- 23 (P less than 0.01) during androgen treatment. No significant effects on levels of IGF-binding protein-I were seen. It is concluded that androgen therapy increases the availability of 1,25-dihydroxyvitamin D and the level of IGF-I, which may be important links in the action of testosterone.

Adolescent↗
PubMed1991

Stable Listeria monocytogenes live vaccine candidate strains with graded attenuation on the mouse model.

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.

Animals↗
PubMed1991

Technological aspect of the production of live dysentery vaccines for oral administration.

An experimental technology for the production of live freeze-dried vaccines prepared from attenuated Shigella flexneri 2a and Shigella sonnei I strains was developed. It is based on the cultivation of bacterial strains in a fermentor under conditions which ensure high yields. The strains grow in S-form, their antigenic structure is preserved and they remain non-virulent. The attenuating markers are stable. The freeze-dried vaccines retain good immunogenicity when applied intra-intestinally to rats.

Administration, Oral↗
PubMed1990

Stable Salmonella live vaccine strains with two or more attenuating mutations and any desired level of attenuation.

Mutants optimally attenuated for highly susceptible hosts and protecting after a single oral vaccination are often overattenuated for host species being less susceptible. Therefore, to select vaccine strains optimally attenuated for the particular host species it is essential that a range of mutants with graded levels of attenuation be provided so as to permit lesser susceptibility to be compensated for by a correspondingly lower level of attenuation. This, while guaranteeing the stability through two-marker or multi-marker attenuation, can be suitably accomplished by slightly to moderately virulence-reducing mutations. Aspartic acid auxotrophy and, in particular, 'metabolic drift' mutations, possibly by additionally incorporating antiepidemic markers, are adopted for the mouse model to demonstrate stepwise production of S. typhimurium and S. typhi vaccine candidate strains with graded attenuation or any level of attenuation desirable. It is emphasized that this basic approach is relevant to practice.

Animals↗
PubMed1990

Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. I. Construction of vaccine candidate strains with retained invasiveness but reduced intracellular multiplication.

Live Shigella flexneri 2a and Shigella sonnei Phase I vaccine candidate strains with two virulence-reducing markers were constructed through stepwise incorporation of weakly attenuating purine auxotrophy with subsequent rifampicin-resistance (RNA polymerase) mutation to yield optimal attenuation. These vaccine candidate strains showed an unaltered plasmid profile; did not cause keratoconjunctivitis in the Sereny test, while being excreted for a short but still marked period and providing partial protection from wild-strain infection; exhibited for guinea-pig conjunctival epithelia, HeLa cells and rat enterocytes a maintained invasiveness with reduced intracellular multiplication with little, if any, reversible cell damage; and produced, just as their ultrasonic lysates, no exudative reaction in the rabbit gut loop test.

Animals↗
PubMed1990

Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. II. Preliminary results of vaccination of adult volunteers and children aged 2-17 years.

Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains were tested for tolerance in 14 adults as well as for tolerance and immunogenicity in children aged 2-17 years. For fresh culture material, the limit for side effects fading within 36 h such as meteorism, loose stools, tenesmus and slight temperature, and tolerated by volunteers was 3 x 10(9) colony-forming units (c.f.u.). Excretion of vaccine strain germs for 2-3 days was observed only at doses of 10(10) c.f.u. and greater (2-3 x 10(10)). Children tolerated up to the maximum dose of 1-3 x 10(9) c.f.u. of the lyophilized vaccine without side effects. No vaccine strain germs were found in faeces, antigen being detected for 4-5 days. The total dose of 1-3 x 10(9) c.f.u. being distributed among three oral inoculations at intervals of 1-2 days induced coproantibodies in 70% of the vaccinees during the first 3 months, and in 30-40% up to 6 months. In contrast, the single application of this total dose for primary immunization, or booster after 10 months, proved to be more efficient. Ninety per cent of the subjects had markedly elevated titres for not less than 6 months.

Adolescent↗
PubMed1990

Potential Shigella flexneri 2a and Shigella sonnei I live vaccinal strains. Characterization of immunogenicity in animal models.

Rats and rabbits were immunized intraintestinally with different doses of virulent and nonvirulent live Shigella flexneri 2a and Shigella sonnei I strains. The nonvirulent strains had one or two attenuating markers. The period of excretion with the faeces of the bacteria and of their polysaccharide antigens, the proliferation of antigen-binding and antibody-producing cells in the spleens and gut-associated lymphoid tissues and the levels of antibodies in sera and faeces were studied. Attenuated strains S. flexneri 2a 77 and S. sonnei I 3359 induced the most potent and long lasting local immune response.

Animals↗
PubMed1990

Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. III. Lipopolysaccharide-specific IgA in the intestine after oral administration of Escherichia coli.

The assumption that local immunologic mechanisms are responsible for findings on the specific microbial colonization of the gastrointestinal tract of mice, is confirmed by results described in the present communication. Quantitative examination of intestinal lavage fluids after oral administration of germs by ELISA showed that (i) there is a critical dose above which a significant increase of IgA synthesis is observable; (ii) low antibody levels could be detected already in the untreated control group. It may be assumed that--regardless of the biological characteristics of the administered strain, namely, substrate and receptor competition--the stimulability of local immunity provides against permanent monocolonization with displacement of the autochthonous Enterobacteriaceae in adult and immunocompetent hosts.

Administration, Oral↗
PubMed1990

Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. I. Influencing the biotope by means of metabolic drift mutants of Escherichia coli.

Through the selection of spontaneous metabolic drift mutants (selection marker RifR) of an Escherichia coli strain (O6:H2 SmR) of known settling capacity in conventional mice, it was attempted to obtain clones with positively optimized in vitro characteristics, which may exert a promotive influence upon the in vivo colonizing behaviour. Using 512 drift mutant strains (E. coli O6:H2 SmR RifR) we were able to establish positive optimizations, at an over-aleatory rate, for each of the in vitro characters tested (haemagglutination capacity of rabbit, guinea pig, and fowl erythrocytes; overgrowing power of mouse-adapted wild-type E. coli strains; formation of biomass with exclusive utilization of dextrose, lactose, fructose, adonitol, salicin, rhamnose, mannose; multiplying power; quantitative motility; and capacity to synthesize mucus). A higher settling rate (larger number of animals in which the test strain shared greater than or equal to 50% of the Enterobacteriaceae population than that obtained with the initial strain) could be established for one out of the 62 clones tested in vivo (a rise from 20% to 55%). The higher settling rate was associated with combinations of various functional parameters and not with an improvement of any of the individual functions. Despite the increase in settling rate relative to the number of experimental animals used in these studies, it was not generally possible to obtain a more than 3 days' dominance of the test strain within the lac+ Enterobacteriaceae. This is considered to be due primarily to the incipient synthesis of secretory IgA.

Administration, Oral↗
PubMed1990

Modulating the microbial colonization of the gastrointestinal tract by oral administration of defined Escherichia coli strains. II. Influencing the biotope by means of geographically unrelated Escherichia coli strains.

An effective increase in the rate of colonization can be accomplished, in analogy with the pathogenetic mechanism of what is known as travelers' disease, through the administration of geographically unrelated strains. As compared to Escherichia coli strains isolated in the GDR, metabolic drift-optimized and Ethiopian strains showed an increase from 20 to 50%. It was not, however, possible to maintain a greater than or equal to 50% share in the population of Enterobacteriaceae over a period of more than up to three days. Immunologic mechanisms are considered to be responsible for this.

Administration, Oral↗
PubMed1988

Local and systemic immune response in rabbits after intraintestinal immunization with a double-marker attenuated strain of Salmonella typhimurium.

Local and systemic immune response was studied in 3 groups of rabbits immunized and reimmunized 190 days later with S. typhimurium double-marker attenuated strain 1,771 and doses ranged from 20.10(9) to 0.2.10(9) cells. Another group of rabbits was immunized with extract (hydroxylammine) vaccine. It was found that the attenuated strain persisted for considerable time in the gut, and induced pronounced and continuous immune response as measured by the passive hemagglutination test. The serum antibody response had the character of a secondary one with switching on the synthesis of IgM to IgG already after basic immunisation. By the Coombs' technique it was shown that specific immunoglobulins demonstrated in feces were secretory antibodies of the class IgA (SIgA). The immune response developed after reimmunization was still more vigorous and prolonged pointing to an immune memory existance. It was possible to obtain well manifested immunity with the lowest dose. The extract vaccine revealed only weak and transitory serum and intestinal antibody levels without SIgA appearance. The results obtained in this setup make S. typhimurium 1771 a perspective candidate for a live vaccine.

Animals↗
PubMed1987

Technological investigations with attenuated strains of Shigella for production of live vaccines. 1. Cultivation in a fermenter of an attenuated strain S. flexneri 2a with two markers.

A method was developed for cultivation of the strain Shigella flexneri 2a 77 with two attenuated markers. It ensures the preservation of the initial properties of the strain. The regimen for control of dissolved oxygen level was optimized. It was established that yeast extract is a necessary component of the nutritive medium used. The role of the phase and quantity of the inoculum for growth of the bacterial population has been clarified. Fresh fermenter culture, applied in rats, shows a high immunogenic activity. After lyophilization, the cultures retain 50-70% of the immunogenic activity of the non-lyophilized cultures. The method makes preconditions for the production of a live attenuated dysentery vaccine for oral administration.

Animals↗