[Problems and prospects of gene therapeutics and DNA vaccines development and application].

The review is summarized foreign publications devoted to different aspects of DNA vaccines and gene therapeutics' biological safety. In spite of incomprehension in their action, numerous prototype DNA-based biopharmaceuticals are in advanced stages of human clinical trials. This review is focused on some safety concerns of gene formulations vaccines relate to toxic effects, vertical transmission possibility, genome integration complications, immunologic and immunopathologic effects and environmental spread. It is noted that necessity of national regulatory documents development related to gene therapy medicinal products is significant condition of their application to medical practice.

[Identification of clinical isolates of Burkholderia cepacia and assessment of their pathogenicity in animal experiments].

In experiments on animals study of pathogenicity of 9 clinical strains of Burkholderia cepacia isolated from patients with chronic lung diseases was performed. Preliminary identification of studied strains by means of biochemical and genetic methods allowed to establish their belonging to B. cepacia species. It was determined that 6 of 9 strains are epidemiologically significant. Experiments showed that bacteria of studied strains are not able to cause infectious process in white mice and hamadryas baboons. Conclusion about appropriateness of development and use of other biological models was made.

[The role of the Yersinia plasmid of calcium-dependency in the formation of the plague immunity].

It was shown that viable variants of the Y. enterocolitica microorganisms containing the plasmid of Ca-dependency (native one or from EV/ I Y. pestis cells) were more immunogenic to plague-infected guinea pigs than isogenic non-plasmid variant. As a result of studying the protective properties of the bacteria Y. enterocolitica sub-cellular fractions it was determined that the largest quantity of immunogen per unit of protein was accumulated in the cultures of bacteria's plasmid variant. The aggregate of the obtained experimental data suggested that there was a non-identified protective antigen (or antigens) for guinea pigs to be encoded by chromosome's DNA. Besides, the Ca-dependency plasmid gene products take part in its excretion and, as the factors of pathogenicity, provide survivability of the Y. enterocolitica microorganisms in the host organism, increasing thus the immunogen accumulation in it.

[The antibody spectrum after the inoculation of sensitive animals with Yersinia pestis and Yersinia pseudotuberculosis bacteria]. / Spektr antitel pri vvedenii chuvstvitel'nym zhivotnym bakterii Yersinia pestis i Yersinia pseudotuberculosis.

Antibody spectra in the sera of guinea pigs and white mice infected with Y. pestis and Y. pseudotuberculosis, the causative agents of plague and pseudotuberculosis, were determined with the use of immunoblotting. The amount of antigens, found to produce humoral immune response both in plague and in pseudotuberculosis was, on the whole, considerably less (5-6 times) in white mice than in guinea pigs. The animals were found to produce antibody response to plasmid-specific (Yop) Y. pestis antigens with with molecular weights 76, 41 and 34 kD and Y. pseudotuberculosis antigens with molecular wt of 41, 34 and 25 kD. Differences in the character of humoral immune response induced in guinea pigs by killed and live Y. pseudotuberculosis were determined. In the animals inoculated with killed bacteria these differences consisted in the absence of antibody formation to the immunodominant antigen with a molecular weight of 62 kD and in the increase of antibody response to antigens with molecular weights of 36 and 21 kD, supposed to be related to Y. pseudotuberculosis pathogenicity factors and to possess protective properties.

[Design of recombinant DNA intended for insertional mutagenesis of bacteria]. / Konstruirovanie rekombinantnhkh DNK, prednaznachennykh dlia insertsionnogo mutageneza bakterii.

The recombinant plasmid pKC47M has been constructed on the base of a mini-Mu-phage and the replicon of plasmid pBR328. The plasmid was constructed for in vivo insertional mutagenesis in bacteria. Use of the plasmid in vivo alleviates the possibility of secondary transposition of the inserted sequences and enrichment of multiple-site mutations. Efficient mutagenesis caused by plasmid pKC47M was tested by induction auxotrophic mutations in Escherichia coli, Yersinia enterocolitica, Yersinia pseudotuberculosis.

[Connection of outer membrane protein composition in Yersinia pestis cells with intrinsic plasmids]. / Sviaz' belkovogo sostava naruzhnykh membran kletok Yersinia pestis s nositel'stvom sobstvennykh plazmid.

A set of isogenic derivatives of Yersinia pestis EV strain was obtained including the variants harbouring the different compositions of Yersinia own plasmids. The protein profiles of outer membranes of the set of strains were defined. The polyacrylamide gel electrophoresis has shown the small 6.1 Md plasmid to code an outer membrane protein with mol mass 29 kDa, different from pesticin I, while the heavy 60.0 Md plasmid encodes the 15-16 kDa polypeptide different from monomers of F1 and T-antigens of plague microbe.