ABSTRACT
DNA viruses have high oncogenic risk viruses; they cause emergence of Kaposi sarcoma, Lymphoma, Squamous cell carcinoma. HIV immunodeficiency promotes increase in frequency of such tumors. Etiotropic therapy of HIV patients considerably reduces prevalence of DNA viruses and a viral malignization.
Subject(s)
Carcinoma, Squamous Cell/epidemiology , DNA Tumor Viruses/isolation & purification , HIV Infections/complications , Lymphoma/epidemiology , Sarcoma, Kaposi/epidemiology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/virology , Face , HIV Infections/drug therapy , Humans , Lymphoma/immunology , Lymphoma/virology , Maxilla , Prevalence , Sarcoma, Kaposi/immunology , Sarcoma, Kaposi/virologyABSTRACT
The development of therapeutic vaccines against chronic hepatitis B is a major challenge facing modern medicine. HBc antigen-expressing DNA-vaccines designed to be transported into the organism by attenuated Salmonella appear to be good candidates for the purpose. Expression of HBc-antigen was earlier shown to lead to the loss of ability of attenuated Salmonella bearing the DNA-vaccine to multiply in the host lymphoid tissue of mice after per rectum immunization and in human monocyte culture. The aim of the study was to assess the influence of HBc-antigen expression on replication of a virulent strain of wild-type Salmonella serotype Enteritidis in the murine lymphoid tissue after per rectum infection and in human blood monocytes. HBc expression was shown to inhibit propagation of Salmonella in both model systems despite its high virulence.
Subject(s)
Hepatitis B Core Antigens/biosynthesis , Salmonella Infections/microbiology , Salmonella/growth & development , Animals , Mice , Salmonella Infections/drug therapy , Salmonella Infections/immunology , Vaccines, DNA/pharmacology , VirulenceABSTRACT
The behavior of S. enteritidis recombinant strain E-23/pKDNA(3.1) with HBc antigen expressed by the eukaryotic promoter (DNA vaccine) in the body of mice after their infection per rectum and in the culture of macrophages was studied. The expression of HBc was shown to lead to the loss of the capacity of salmonellae for persistence in parenteral lymphoid tissue and for inducing the formation of anti-HBc antibodies. The study of the interaction of salmonellae with the macrophage culture revealed that the synthesis of HBc antigen inhibited the intracellular multiplication of salmonellae.
Subject(s)
Genetic Vectors/physiology , Monocytes/microbiology , Phagocytosis , Salmonella enteritidis/physiology , Administration, Rectal , Animals , Cells, Cultured , Genetic Vectors/immunology , Genetic Vectors/metabolism , Hepatitis B/prevention & control , Hepatitis B Core Antigens/biosynthesis , Humans , Intestines/microbiology , Lymph Nodes/microbiology , Mesentery/immunology , Mice , Salmonella enteritidis/immunology , Salmonella enteritidis/metabolism , Spleen/microbiology , Time Factors , Vaccines, Synthetic/administration & dosage , Viral Hepatitis Vaccines/administration & dosageABSTRACT
Data about ongoing researches in order to increase efficacy and immunogenicity of licensed hepatitis B vaccines and to develop new therapeutic vaccines for chronic hepatitis B treatment are reviewed.
Subject(s)
Hepatitis B/prevention & control , Hepatitis B/therapy , Vaccination/methods , Viral Hepatitis Vaccines/immunology , Adult , Animals , Chronic Disease/therapy , Genetic Vectors , Humans , Infant , Lipoproteins/immunology , Lipoproteins/therapeutic use , Salmonella/genetics , Salmonella/metabolism , Vaccines, DNA/immunology , Viral Hepatitis Vaccines/therapeutic use , Viral Proteins/biosynthesis , Viral Proteins/geneticsABSTRACT
Designing of a therapeutic vaccine for patients with chronic hepatitis B is a task of contemporary medicine. The natural way of administering the vaccine is the most attractive and inexpensive immunization variant. The use of attenuated strain Salmonella as a carrier of the virus antigen fits the purpose. With this idea in mind, the potentialities of the recombinant attenuated strain Salmonella Enteritidis E-23/pKHBc to replicate in the intestine, mesenteric nods and spleen of mice and to stimulate the immune response to HBc-antigen after its rectal administration (as suppositories) in mice were investigated. It was shown that the recombinant strain is discharged from the intestine within 6 hours after immunization, whereas, it is discharged on day 2 after immunization from the lymphatic nods and is traced there during the 5 subsequent days. Besides, the recombinant strain also possessed the possibility to persist in the spleen of mice for 42 days and to induce there the formation of antibodies to HBc-antigen.
Subject(s)
Hepatitis B Core Antigens/immunology , Hepatitis B Vaccines/administration & dosage , Salmonella Vaccines/administration & dosage , Salmonella enteritidis/immunology , Administration, Rectal , Animals , Hepatitis B Core Antigens/biosynthesis , Hepatitis B Core Antigens/genetics , Hepatitis B Vaccines/immunology , Immunotherapy, Active/methods , Lymphoid Tissue/immunology , Lymphoid Tissue/microbiology , Mice , Salmonella Vaccines/immunology , Salmonella enteritidis/genetics , Suppositories , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunologyABSTRACT
A variety of approaches to creating vaccines against the HIV-infection are discussed in the paper. It is demonstrated that vaccines can be used both for treatment and prevention. They can be synthetic, DNA-vaccines and vector-type ones based on the attenuated recombinant strain of Salmonella. Apart from gp120, reverse transcriptase and tat-gene products can be used as the antigen.
Subject(s)
AIDS Vaccines/administration & dosage , Acquired Immunodeficiency Syndrome/immunology , AIDS Vaccines/genetics , Acquired Immunodeficiency Syndrome/genetics , DNA, Viral/genetics , HumansABSTRACT
Studies of human microflora in health and disease and during exposure to professional and ecological factors is a traditional problem solved for many years by staff members of Department of Microbiology with Virology and Immunology, I. M. Setchenov Moscow Medical Academy. The purpose of research is to develop methods and means for diagnosis and prevention of human microbiocenosis disorders. Fundamental and applied research in cooperation with prophylactic and clinical institutions and departments yielded data contributing to solution of many pressing problems in prevention and diagnosis of infectious diseases.
Subject(s)
Academies and Institutes , Allergy and Immunology/education , Ecology , Ecosystem , Microbiology/education , Virology/education , Humans , Infection ControlABSTRACT
In this work the results of obtaining HBcAg-producing attenuated Salmonella strains, serovars S. enteritidis and S. typhimurium, and their comparative study is presented. As revealed in this study, attenuated S. enteritidis strain E-23 and S. typhimurium strain T-10, producing HBcAg, induce cell-mediated and humoral immune response to HBcAg after injected into anovals. After injection S. typhimurium strain T-10 induces a much higher titer of specific antibodies than S. enteritidis strain E-23. The level of specific antibodies induced by recombinant HBcAg seems to correlate with the capacity of salmonellae for survival inside macroorganisms.
Subject(s)
Antigen Presentation , Hepatitis B Core Antigens/immunology , Salmonella enteritidis/immunology , Salmonella typhimurium/immunology , Animals , Genetic Vectors/immunology , Hepatitis B/immunology , Hepatitis B/prevention & control , Hepatitis B Core Antigens/genetics , Hepatitis B Vaccines/genetics , Hepatitis B Vaccines/immunology , Immunity, Mucosal , Mice , Mice, Inbred BALB C , Plasmids/genetics , Recombination, Genetic , Salmonella enteritidis/genetics , Salmonella typhimurium/genetics , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunologyABSTRACT
The availability of bacterial genome sequences raises an important new problem - how can one move from completely sequenced microorganisms as a reference to the hundreds and thousands of other strains or isolates of the same or related species that will not be sequenced in the near future? An efficient way to approach this task is the comparison of genomes by subtractive hybridization. Recently we developed a sensitive and reproducible subtraction procedure for comparison of bacterial genomes, based on the method of suppression subtractive hybridization (SSH). In this work we demonstrate the applicability of subtractive hybridization to the comparison of the related but markedly divergent bacterial species Escherichia coli and Salmonella typhimurium. Clone libraries representing sequence differences were obtained and, in the case of completely sequenced E. coli genome, the differences were directly placed in the genome map. About 60% of the differential clones identified by SSH were present in one of the genomes under comparison and absent from the other. Additional differences in most cases represent sequences that have diverged considerably in the course of evolution. Such an approach to comparative bacterial genomics can be applied both to studies of interspecies evolution - to elucidate the "strategies" that enable different genomes to fit their ecological niches - and to development of diagnostic probes for the rapid identification of pathogenic bacterial species.
Subject(s)
Escherichia coli/genetics , Genome, Bacterial , Salmonella typhimurium/genetics , Base Sequence , DNA Primers , Nucleic Acid Hybridization , Subtraction TechniqueSubject(s)
Bacterial Vaccines , Genetic Vectors , Salmonella/immunology , Vaccines, Synthetic , Animals , Antibodies, Bacterial/biosynthesis , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Bacterial Vaccines/immunology , Bacterial Vaccines/therapeutic use , Drug Design , Genes, Bacterial , Genetic Engineering , Humans , Salmonella/genetics , Salmonella/pathogenicity , Salmonella Infections/prevention & control , Salmonella Infections, Animal/prevention & control , Vaccines, Attenuated , VirulenceSubject(s)
Drug Design , Typhoid-Paratyphoid Vaccines/immunology , Adult , Animals , Antigens, Bacterial/immunology , Child , Humans , Mutation , Polysaccharides, Bacterial/immunology , Salmonella typhi/genetics , Salmonella typhi/immunology , Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines/adverse effects , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunologySubject(s)
Bacterial Vaccines , Genes, Bacterial , Salmonella/genetics , Salmonella/immunology , Animals , Bacterial Vaccines/genetics , Bacterial Vaccines/immunology , Bacteriological Techniques , Cyclic AMP/analysis , Humans , Mice , Mutation , Salmonella typhimurium/genetics , Salmonella typhimurium/immunologyABSTRACT
The Salmonella typhimurium B-2/1 double mutant with cya and crp mutations was obtained by a recombination process. The mutant exhibited a low virulence and inability to utilize citrate. In terms of these properties, the mutant differs from the wild-type strain. The mutant is able to persist in the body of mice, cattle, and monkeys, provoking the immune response to its oral administration.
Subject(s)
Bacterial Vaccines/genetics , Salmonella typhimurium/genetics , Vaccines, Synthetic/genetics , Administration, Oral , Animals , Bacterial Vaccines/administration & dosage , Bacterial Vaccines/immunology , Cattle , Mice , Mutation , Papio , Salmonella typhimurium/immunology , Salmonella typhimurium/pathogenicity , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , VirulenceSubject(s)
Enterobacteriaceae/genetics , Gene Expression Regulation, Bacterial/genetics , Genes, Bacterial , Receptors, Cyclic AMP/genetics , Cyclic AMP/metabolism , Enterobacteriaceae/metabolism , Enterobacteriaceae/pathogenicity , Gene Expression Regulation, Bacterial/physiology , Genes, Bacterial/physiology , Mutation , Receptors, Cyclic AMP/metabolismSubject(s)
Salmonella/pathogenicity , Animals , Antigens, Bacterial/genetics , Antigens, Bacterial/toxicity , Bacterial Vaccines/immunology , Enterotoxins/genetics , Enterotoxins/toxicity , Humans , Mutation , Plasmids/genetics , Salmonella/genetics , Salmonella/immunology , Salmonella Infections, Animal/etiology , Salmonella Infections, Animal/prevention & control , Virulence/geneticsABSTRACT
To study the role of cAMP in the virulence of S. typhimurium, cAMP-producing plasmid pTG 4 was transferred to cAMP-deficient S. typhimurium mutant. The transfer of the plasmid enhanced the virulence of the microorganisms due to the increased destruction of macrophages and the intensified multiplication of salmonellae in the spleen of mice.
Subject(s)
Cyclic AMP/physiology , Salmonella typhimurium/pathogenicity , Animals , Macrophages/physiology , Mice , VirulenceABSTRACT
The changes in cAMP levels in spleen macrophages of mice infected with low-virulent and virulent Salmonella strains and the effect of propranolol on Salmonella reproduction in the spleen, and the outcome of Salmonella-induced infection have been studied. A persistent increase in cAMP levels in spleen macrophages during Salmonella infection caused by virulent Salmonella strains has been demonstrated. Low-virulent Salmonella strains failed to cause the elevation of cAMP levels in spleen macrophages. Propranolol injection to mice prevented intensive Salmonella reproduction in the spleen and diminished the animal mortality rate.
Subject(s)
Cyclic AMP/physiology , Salmonella Infections, Animal/etiology , Animals , Cyclic AMP/analysis , Drug Evaluation, Preclinical , Macrophages/analysis , Mice , Mice, Inbred CBA , Propranolol/therapeutic use , Salmonella/pathogenicity , Salmonella Infections, Animal/drug therapy , Salmonella Infections, Animal/microbiology , Spleen/analysis , Spleen/microbiology , VirulenceABSTRACT
The effect produced on the course of Salmonella infection in mice by the removal of peritoneal macrophages with agarose has been studied. Peritoneal macrophages have been shown to control the multiplication of faintly virulent and virulent S. typhimurium strains in the spleen of mice. In immune mice the elimination of the virulent strain of the causative agent of superinfection may occur without the control of peritoneal macrophages.