Experimental study of the protective activity of vaccines made from 7 Pseudomonas aeruginosa immunotypes

Monovaccines were prepared from seven P. aeruginosa immunotypes (according to Fisher's classification) and three P. aeruginosa production strains belonging to immunotypes 2, 3, and 7. The immunogenic potency of these monovaccines was studied in direct and cross experiments on the active protection of mice. The study revealed that the monovaccines prepared from P. aeruginosa of seven immunotypes possessed both specific and cross protective activity. Protective cross activity was revealed also in the vaccines prepared from the production strains. When tested in mice challenged with the corresponding homologous strains, the monovaccines prepared from immunotypes 2, 3, 4 and 7 proved to possess higher immunogenic potency than monovaccines prepared from immunotypes 1, 5 and 6.     

The immunogenicity of mono- and associated vaccines made from strains of opportunistic bacteria]

In experiments on white mice the immunogenic potency of two variants of combined vaccines prepared from strains of opportunistic bacteria was compared with that of monovaccines used as the components of the combined vaccines. All the vaccines under study were found highly immunogenic. Decrease of monovaccine share in the combined vaccine did not reduce the immunogenic potency to any of the strains. An 8- to 16-fold increase in the level of specific antibodies in the colostric lactosera of cows immunized with combined vaccines was observed, and the survival rate of newborn calves increased 3- to 4-fold.     

Experimental study of the immunogenicity of a monopreparation of Klebsiella pneumoniae antigen complex and its association with Staphylococcus, Proteus and Escherichia coli antigens

The study carried out in mice with experimental Klebsiella sepsis has revealed that Staphylococcus, Proteus and E. coli antigenic complexes used as monovaccines ensure the protection of a definite percentage of the animals from K. pneumoniae infection. The mixture of these 3 preparations possesses a higher protective potency. The immunogenic potency of K. pneumoniae antigenic complex used as a component of combined vaccines with 2 or 4 components has proved to be sufficiently high and not inferior to the potency of K. pneumoniae monovaccine.     

Progression of coronary atherosclerosis relates to the onset of myocardial infarction in an animal model of spontaneous myocardial infarction (WHHLMI rabbits).

Recently, we developed myocardial infarction-prone WHHLMI rabbits from coronary atherosclerosis-prone WHHL rabbits (WHHLCA rabbits) by selective breeding. In this study, we examined the relation of atherosclerotic plaques to the onset of myocardial infarction. We examined myocardial lesions of 378 WHHL rabbits born between 1992 and 2000, and atherosclerosis lesions of 93 WHHLCA and 82 WHHLMI rabbits. The aortic lesions were evaluated as percent surface lesion area. The coronary lesions were evaluated as cross sectional narrowing using sections prepared at 500 or 1,000 microm intervals. Serum lipid levels were assayed with enzymatic methods. The cumulative incidence of fatal myocardial infarction between 11 and 35 months old was 90% in WHHLMI rabbits and 21% in WHHLCA rabbits, respectively. Selective breeding increased the serum cholesterol levels by about 200 mg/dl despite there being no changes in triglyceride levels. Aortic and coronary atherosclerosis progressed markedly in WHHLMI rabbits compared to WHHLCA rabbits. Especially, WHHLMI rabbits over 15 months old showed more than 90% cross sectional narrowing of the left circumflex arteries, main stem of the left coronary artery, and the origin portion of the right coronary artery. In addition, there were no gender differences in atherosclerotic lesions of both aortas and coronary arteries. In conclusion, the present study showed that marked progression of coronary atherosclerosis was probably associated with spontaneous development of myocardial infarction in WHHLMI rabbits.     

Elevated levels of a calcium-activated muscle protease in rapidly atrophying muscles from vitamin E-deficient rabbits.

A Ca2+-activated proteolytic enzyme that partially degrades myofibrils was isolated from hind limb muscles of normal rabbits and rabbits undergoing rapid muscle atrophy as a result of vitamin E deficiency. Extractable Ca2+-activated protease activity was 3.6 times higher in muscle tissue from vitamin E-deficient rabbits than from muscle tissue of control rabbits. Ultrastructural studies of muscle from vitamin E-deficient rabbits showed that the Z disk was the first myofibrillar structure to show degradative changes in atrophying muscle. Myofibrils prepared from muscles from vitamin E-deficient rabbits showed partial or complete loss of Z-disk density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the amount of troponin-T (37 000 daltons) and alpha-actinin (96 000 daltons) was reduced in myofibrils from atrophying muscle as compared to myofibrils prepared from control muscle. In vitro treatment of purified myofibrils with purified Ca2+-activated proteolytic enzyme produced alterations in myofibrillar ultrastructure that were identical to the initial alterations occurring in myofibrils from atrophying muscle (i.e. weakening and subsequent removal of Z disks). Additonally the electrophoretic banding pattern of Ca2+-activated proteolytic enzyme-treated myofibrils is very similar to that of myofibrils prepared from muscles atrophying as a result of nutritional vitamin E deficiency. The possible role of Ca2+-activated proteolytic enzyme in disassembly and degradation of the myofibril is discussed.     

The preparation and chemical composition of fractions from Aspergillus fumigatus wall and protoplasts possessing antigenic activity.

A detergent-soluble fraction was prepared from the fragmented wall of Aspergillus fumigatus mycelium using the non-ionic detergent Triton X-100, and a wall-free extract was prepared from the same source in the form of protoplasts, released by a lytic enzyme system from Trichoderma harzianum. These extracts were examined by polyacrylamide gel electrophoresis and their detailed chemical composition was established. They were compared with the water-soluble fraction prepared from total mycelium, which is used routinely in this laboratory for serological tests. All fractions had immunological reactivity towards an antiserum prepared in rabbits against this water-soluble fraction of the mycelium, as shown by double diffusion. Both protein and carbohydrate moieties appear to be involved in the antigenic sites, with carbohydrate reactivity predominantly associated with the protoplast fraction. The fact that all preparations contained at least one common antigenic determinant, as judged by lines of identity to a single antiserum, is discussed in relation to antigen location.     

Stimulation of colonic goblet cells by cecal filtrates from rabbits with experimental mucoid enteropathy

Mucoid enteropathy was induced experimentally by ligation of the cecum, and sterile filtrates were prepared from cecal contents of sick and control rabbits. Explants were prepared from the colons of normal rabbits and were maintained in a short-term organ culture system. Cecal filtrates from rabbits with experimental mucoid enteropathy when added to the culture medium, stimulated mucus secretion and discharge from goblet cells. This was exhibited by an increase in number of visible goblet cells, presence of mucus in crypt lumen and/or presence of a significant amount of mucus blanketing the surface epithelium. The results indicated that a mucus-stimulating substance, a goblet cell secretagogue, was produced in the cecum of affected rabbits.     

The determination of the optimal inoculation dose of an oral cholera chemical bivalent vaccine in a controlled experiment

276 volunteers aged 19 years and over were placed under observation in the course of the trial of oral cholera vaccine in tablets, containing choleragen toxoid, O-antigens of serovars Inaba and Ogawa and a number of Vibrio cholerae exoenzymes, for safety, reactogenic properties and immunological effectiveness. The vaccine was found to produce no reactions in a dose of 1-4 tablets; the administration of 3 tablets (300,000 binding units of the toxoid and 10,000 units of O-antigens, serovars Inaba and Ogawa) was shown to induce the most intensive synthesis of both antitoxins and vibriocidal antibodies in the blood sera of volunteers, as well as IgA coproantibodies. The oral vaccine was found to have an advantage over parenteral vaccines due to the absence of reactogenic properties and the formation of local immunity: coproantibodies appeared in 80% and 9% of the vaccinees respectively.     

Comparative study of smallpox vaccines from strains B-51, EM-63 and L-IVP in a controlled epidemiologic trial. I. Reactogenic characteristics of the smallpox vaccines]

A comparative study of smallpox vaccines prepared from the l-ivp zm-63 and b-51 strains was carried out under conditions of controlled epidemiological trial. Children subject to planned vaccination were scarified with commercial batches of the preparations under study (with the same infectious activity). As a result of investigations it was found that in the group of those scarified with the vaccine from zm-63 strain strong local and catarrhal reactions and some disturbances of general condition were more frequent than in those scarified with preparations from the l-ivp and b-51 strain. Along with this, the temperature elevation of various intensity showed no statistically significant difference in the groups a vaccinated with the vaccines compared. Integral analysis of signs characterising different manifestations of reactigenic properties of the vaccines compared led to the conclusion that preparations made of zm-6 strain had greater reactogenic properties.     

A novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit

Treatment of low density lipoprotein (LDL) receptor-deficient rabbits (WHHL rabbits) with probucol (1% w/w in a chow diet) lowered their LDL-cholesterol levels by 36%, consonant with the reported effectiveness of the drug in patients deficient in the LDL receptor. Initial studies of LDL fractional catabolic rate (FCR) using 125I-labeled LDL prepared from the serum of untreated WHHL rabbits showed no difference between probucol-treated WHHL rabbits and untreated WHHL rabbits. When, however, 125I-labeled LDL was prepared from donor WHHL rabbits under treatment with probucol and injected back into them, the FCR was found to be increased by about 50% above that measured simultaneously using 131I-labeled LDL prepared from untreated WHHL donors. The labeled LDL from probucol-treated donors was also metabolized more rapidly than that from untreated donors when injected into untreated WHHL rabbits or into untreated wild-type New Zealand White rabbits. Finally, it was shown that rabbit skin fibroblasts in culture degraded labeled LDL prepared from probucol-treated WHHL rabbits more rapidly than that prepared from untreated WHHL donors. This was true both for normal rabbit fibroblasts and also for WHHL skin fibroblasts, although the absolute degradation rates in the latter were, of course, much lower for both forms of LDL. The data indicate that a major mechanism by which probucol lowers LDL levels relates not to changes in the cellular mechanisms for LDL uptake or to changes in LDL production but rather to intrinsic changes in the structure and metabolism of the plasma LDL of the probucol-treated animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the reactogenic and immunogenic properties of meningococcal vaccines

The results of the study of the reactogenic and immunogenic properties of meningococcal polysaccharide A + C vaccine in the controlled epidemiological trial, with regard to variations depending on the initial immunological characteristics of vaccinees in terms of the levels of antibodies to the polysaccharides contained in the vaccine, are presented. The study was made on school children: 303 of them were immunized with the meningococcal vaccine under test, and 229 (controls) with adsorbed diphtheria-tetanus toxoid. This study revealed that the reactogenic properties of the preparation were more pronounced in those children whose blood sera had been found to contain no antibodies to polysaccharides A and C prior to immunization. The immunological properties were more pronounced with respect to polysaccharide A. The titer of antibodies to polysaccharide A was found to depend on the previous immunological status of the child, which was indicative of the booster effect produced by the vaccine. The data obtained in the study suggest that the evaluation of the reactogenic and immunogenic properties of newly developed prophylactic preparations should be made with due regard for the previous immunological status of vaccinees in respect to the antigens contained in the meningococcal vaccine under test.     

Safety and reactogenicity of a group-A meningoccal polysaccharide vaccine for children 5 to 14

The safety and reactogenicity of group A meningococcal polysaccharide vaccine prepared at the G. N. Gabrichevsky Research Institute for Epidemiology and Microbiology (Moscow) and intended for the immunization of children aged 5-14 years were studied. The data obtained in this study made it possible to characterize the preparation as safe and mildly reactogenic. Shifts in the blood formula registered 24 hours after the injection of the vaccine remained within the limits of physiological fluctuations. Subfebrile temperature persisting for 2 days was registered in some of the children aged 5-8 years. Local reaction in the form of hyperemia at the site of injection was insignificant. The optimum vaccination dose will be determined on the basis of the whole complex of the data presented in this work, as well as the data on the immunological activity of the preparation.     

Elevated levels of a calcium-activated muscle protease in rapidly atrophying muscles from vitamin E-deficient rabbits

A Ca²⁺-activated proteolytic enzyme ¹ that partially degrades myofibrials was isolated from hind limb muscles of normal rabbits and rabbits undergoing rapid muscle atrophy as a result of vitamin E deficiency. Extractable Ca²⁺-activated protease activity was 3.6 times higher in muscle tissue from vitamin E-deficient rabbits than from muscle tissue of control rabbits. Ultrastructural studies of muscle from vitamin E-deficient rabbits showed that the Z disk was the first myofibrillar structure to show degradative changes in atrophying muscle. Myofibris prepared from muscles vitamin E-deficient rabbits showed partial or complete loss of Z-disk density. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the amount of troponin-T (37 000 daltons) and α-actinin (96 000 daltons) was reduced in myofibrils from atrophying muscle as compared to myofibrils prepared from control muscle. In vitro treatment of purified myofibrils with purified Ca²⁺-activated proteolytic enzyme produced alterations in myofibrillar ultrastructure that were identical to the initial alterations occuring in myofibrils from atrophying muscle (i.e. weakening and subsequent removal of Z disks). Additionally the electrophoretic banding pattern of Ca²⁺-activated proteolytic enzyme-treated myofibrils is very similar to that of myofibrils prepared from muscles atrophying as a result of nutritional vitamin E deficiency. The possible role of Ca²⁺-activated proteolytic enzyme in disassembly and degradation of the myofibril is discussed.     

Immune response of noninbred mice to subvirion influenza vaccines with various antigen and sorbent loads

The variants of splitted and subunit influenza monovaccines from virus strains A/Leningrad/385/80R (H3N2) and A/Kiev/59/79R (H1N1), adsorbed on aluminium hydroxide and having the varying content of hemogglutinin and the carrier, have been studied. The immune response of noninbred mice to a single and double injections of these vaccines have been evaluated, the concentrations of the antigen and the carrier inducing a high response in the animals, have been determined. Differences in the immunological potency of hemagglutinins H1 and H3 have been noted.     

Efficacy of antibiotics A204 sodium A28695A, and A204np against Coccidia of rabbits.

Three polycyclic, polyether, monocarboxylic acid antibiotics produced by and extracted from a strain of Streptomyces albus and designated A204 sodium, A28695A, or A204-np, were specifically tested for activity against hepatic and incidentally against intestinal coccidia of rabbits. All were effective in preventing infections and acceptable to young rabbits when prepared in pelleted feed. Weight gain, however, was not as good as inoculated, medicated rabbits as in noninoculated, nonmedicated controls. No gross pathologic changes were detected except in the livers of inoculated, nonmedicated controls which were severely infected on greatly enlarged. Livers of medicated rabbits were uninfected and normal in appearance and size.     

Efficacy of Antibiotics A204 Sodium, A28695A, and A204np against Coccidia of Rabbits

SYNOPSIS. Three polycyclic, polyether, monocarboxylic acid antibiotics produced by and extracted from a strain of Streptomyces albus and designated A204 sodium, A28695A, or A204np, were specifically tested for activity against hepatic and incidentally against intestinal coccidia of rabbits. All were effective in preventing infections and acceptable to young rabbits when prepared in pelleted feed. Weight gain, however, was not as good in inoculated, medicated rabbits as in noninoculated, nonmedicated controls.
No gross pathologic changes were detected except in the livers of inoculated, nonmedicated controls which were severely infected and greatly enlarged. Livers of medicated rabbits were uninfected and normal in appearance and size.     

Transfer of osteosarcoma-specific cell-mediated immunity in hamsters by rabbit dialyzable leukocyte extracts

We have investigated the transfer of specific cell-mediated immunity (CMI) to osteosarcoma-associated antigens (OSAA) to hamsters with dialyzable leukocyte extracts (DLE) from OSAA-immunized rabbits. The transfer of specific CMI was determined by leukocyte adherence inhibition (LAI) assay and skin testing. DLE was prepared from rabbits immunized with OSAA, purified protein derivative (PPD), or fibrosarcoma cell plasma membrane preparation (FSM). Control DLE was prepared from rabbits injected with 0.85% NaCl. Significant leukocyte adherence inhibition was observed with leukocytes from hamsters that had received OSAA-specific, PPD-specific, and FSM-specific rabbit DLE, when OSAA, PPD, and FSM were used as antigens, respectively. Similarly, significant ear swelling after injection of OSAA, PPD, or FSM was observed only in hamsters that had received DLE from rabbits immunized with OSAA, PPD, or FSM, respectively. These results suggest that CMI specific for OSAA, PPD, or FSM can be transferred to normal hamsters by DLE from immunized rabbits.     

Studies on the site of origin of the androgen binding protein present in epididymal cytosol from mature intact rabbits

An examination of the site of origin of the 17β-hydroxy-5α-androstan-3-one (5αDHT) binding protein that exists in cytosol prepared from the caput epididymidis from sexually-mature intact rabbits was approached in the following way: Rabbits a) had the ductuli efferent es unilaterally ligated, b) were hemicastrated, c) were made unilaterally cryptorchid. These procedures were designed to decrease or eliminate the flow of testicular fluid into the epididymis. When this occurred, there was a marked decrease or total elimination of 5αDHT binding to cytosol prepared from the caput from the experimental epididymis, as compared to cytosol from the contralateral control side. These results suggest that the 5αDHT binding moiety in cytosol prepared from the caput epididymidis from intact sexually-mature rabbits is of testicular origin and is not the target tissue “receptor.”     

The characteristics of the reactogenicity and immunological activity of a new cholera bivalent chemical vaccine based on the results of controlled trials]

The reactogenic properties and immunological potency of modified cholera chemical vaccine (choleragen-toxoid + O-antigens Inaba and Ogawa) were tested in 278 volunteers aged 18 years and over in comparison with those of a commercial batch of monovalent cholera vaccine (choleragen-toxoid + O-antigen Inaba). The cholera vaccine, enriched with O-antigen Ogawa, was found to be safe; vaccination with this vaccine was not accompanied by the development of systemic and local reactions whose frequency and intensity met the requirements for the reactogenic properties of commercial cholera vaccine. The immunological potency of the bivalent vaccine with respect to strain Inaba was not inferior to that of the commercial vaccine; at the same time in persons immunized with the new preparation the titers of vibriocidal antibodies to strain of serovar Inaba were five-fold higher. The conclusion on the expediency of using cholera chemical vaccine enriched with O-antigen Ogawa was made.     

Interaction of rabbit lymph node cells with bacteria (Salmonella paratyphi B)

In five rabbits immunized withSalmonella paratyphi B antigen in all four paws, incubation of the regional lymph node cells with the same bacteria was followed by a significant shift of some of the bacteria from the supernatant of the culture medium to the sediment (as compared with the controls). In six rabbits, bactericidal activity was demonstrated in extracts prepared from the regional lymph nodes only 30 hours after immunization. No antibodies were present in extracts from control rabbits up to the fifth day after immunization.