[Development of antileprosy vaccines].

The absence of an effective antileprosy vaccine, capable of preventing the spread of leprosy hinders its control in endemic countries. Developing such a vaccine is highly difficult due to the absence of reproducible methods for the in vitro cultivation of Mycobacterium leprae. The results of field trials of earlier proposed vaccines (BCG and BCG in combination with killed M. leprae) are indicative of their insufficient efficacy. The article presents a review of literature, including historical information, current problems and the main approaches to the development of vaccine against leprosy.

[Detection of antibodies to M. leprae in saliva of lepric patients].

Saliva of 116 lepric patients were scanned for antibodies in ELISA (with M. leprae cultivated in vitro used as antigen) in order to work out an invasion-free diagnostic tool for lepra. The ELISA findings for "saliva-serum" pairs from same patients showed an increased level of antibodies both in serum and saliva in 39.7% of cases, and matching of results (positive and negative ones) was observed in 73.3% of patients. The increasing level of specific antibodies as observed in intensification of the lepric process in blood serum occurred simultaneously with its increase in saliva. The invasion-free diagnostics of lepra is promising for examinations of contact persons and of population in endemic regions as well as for evaluating the efficiency of the antilepric therapy.

[Comparative characterization of the antigenic composition of M. leprae and M. lufu]. / Sravnitel'naia kharakteristika antigennogo sostava M. leprae i M.lufu.

The antigenic structure of M. leprae and M. lufu was comparatively studied for the first time. M. lufu was found to have M. leprae-specific protein with a molecular weight of 36 kDa. M. leprae and M. lufu were similar in their fractional composition of proteins and an antibody response to determinants with equal molecular weights in patients with different forms of leprosy and its varying severity. The findings may improve a diagnostic system in leprosy by using M. lufu antigens as an alternative.

[The comparative cultural-biochemical and immunochemical identification of laboratory strains of cultured mycobacteria from leprous patient lesions and from soil]. / Sranitel'naia kul'tural'no-biokhimicheskaia i immunokhimicheskaia identifikatsiia laboratornykh shtammov kul'tiviruemykh mikobakterii iz leproznykh porazhenii bol'nykh i pochvy.

The paper presents the results of studied of cultural biochemical and immunochemical properties of the cultured mycobacteria isolated from patients with leprous lesions of (M.01, M.011) and the soil (M. lufu) in compared to other well-known mycobacteria and between them. M.01, M.011, and M. lufu differ from other representatives of the genus Mycobacterium, but they are close to each other in their cultural biochemical and immunochemical properties, antigenic composition, and protein spectra. The findings are an additional characteristic of the biological properties of M.01, M.011, and M. lufu.

[The identification of the antigenic determinants of Mycobacterium leprae passed through laboratory animals by using monoclonal antibodies]. / Identifikatsiia antigennykh determinant Mycobacterium leprae, passiruemykh na laboratornykh zhivotnykh, s pomoshch'iu monoklonal'nykh antitel.

The antigenic preparations of M. leprae isolated from the biopsy leproma material of leprosy patients, M. leprae obtained by passage through laboratory animals (armadillos, rats) and M. lepraemurium have been identified by indirect solid-phase enzyme immunoassay. Experiments made with the use of the set of monoclonal antibodies (McAb) to different M. leprae antigenic determinants, supplied by the WHO Bank of Monoclonal Antibodies (IMMLEP), have demonstrated the presence of common antigenic determinants in 65-kD protein of M. leprae obtained by passage through armadillos and rats and M. lepraemurium, as well as in 12-kD protein of M. leprae isolated from armadillos and rats and M. leprae isolated from the biotic material of human lepromas. The passage of M. leprae through experimental animals leads to the appearance of a new antigenic determinant in their structure, which is recognized by McAb 111E4.

[The isolation of monoclonal antibodies to strains of Mycobacterium leprae passed through laboratory animals]. / Poluchenie monoklonal'nykh antitel k shtammam mikobakterii lepry, passiruemym na laboratornykh zhivotnykh.

Hybridoma synthetizing monoclonal antibodies (mAB) IIIE4 has been obtained in hybridization of myeloma P3-X63-Ag8. 653 cells and splenocytes from BALB/c mice immunized with M. leprae passaged on rats. The mAB specificity evaluated by enzyme immunoassay using ultrasonic disintegrates of M. leprae obtained from human, Dasypus novemcinctus, rat lepromas as well as mycobacteria of 7 species and E. coli indicated that the mAB reacted only with mycobacteria passaged on the rats. They had weak cross reactivity with M. avium.

[Use of tuftsin in experimental leprosy]. / Primenenie taftsina v éksperimental'noi leprologii.

The effect of tuftsin was studied in vivo using CBA mice infected with M. leprae by Shepard's technique and in vitro using macrophage-like cell line P. 388 (Co-cultivated with M. leprae) and the cultivated leproma tissue. It was found out that tuftsin acted as a stimulator of M. leprae multiplication in foot-pads of mice and as a prolongator of M. leprae survival in the cells of macrophage-like cell line P .388. It is concluded that using tuftsin might be useful in view of studying different aspects of experimental leprosy.

[Immunologic indices in a varying course of lepromatous leprosy]. / Immunologicheskie pokazateli pri razlichnom techenii lepromatoznoi lepry.

The study of the proliferative and regulatory functions of lymphocytes in patients with lepra of the lepromatous type has shown that at the active stage of the disease both the response of lymphocytes to mitogens and their suppressor functions are decreased. During the regression of the disease these characteristics are restored to the normal level only in patients with the relapse-free course of the disease, while patients with relapses in their medical history retain the low level of such characteristics. It is expedient to use these cell-mediated immunity characteristics as signs permitting the formation of risk groups of patients who may expect the relapse of the disease.

[Morphologic characteristics of leproma cell cultures from humans and experimental animals and the effect on them of antileprotic preparations]. / Morfologicheskaia kharakteristika kul'tur kletok leprom cheloveka i éksperimental'nykh zhivotnykh i vliianie na nikh protivoleproznykh preparatov.

Leproma pieces obtained from leprosy patients and M. leprae-infected animals were cultivated by the method of primary explantation. It is noted that the development of a monolayer from macrophages overloaded with M. leprae is a characteristic common to the lepromas of various origin. Antileprosy activity of the drugs under study was assessed by the rate of decrease in mycobacterial load of macrophages. Species features of cultivated lepromas from man, nine-banded armadillo and mouse are characterised. While cultivating lepromas from leprosy patients the peculiarities of tissue culture organization are found out representing immune status and prognosis of specific therapy.

[Functional characteristics of the antioxidative system in mycobacteria grown on perfluorodecalin-modified media]. / Osobennosti funktsionirovaniia antiokislitel'noi sistemy mikobakterii, vyrashchennykh na sredakh, modifitsirovannykh perftordekalinom.

The growth of mycobacteria on perfluorodecalin-modified media was shown to be accompanied by distinct alterations in the activity of the antioxidant enzyme system in M. bovis BCG and M. lufu. In M. bovis BCG the levels of glutathione transferase and glutathione peroxidase-hydrogen peroxidase activity are decreased by 45.47% and 100.88%, respectively. In M. lufu, on the contrary, the level of superoxide dismutase is increased by 42.23%, with no changes observed in the levels of glutathione transferase and glutathione peroxidases. The data obtained suggest physiological heterogeneity of mycobacteria and, thus, open prospects for the differential approaches to the problem of increasing the efficacy of in vitro cultivation of various mycobacterial species, including M. leprae.

[Evaluation of the functional state of the leprous macrophages]. / Otsenka funktsional'nogo sostoyaniya leproznykh makrofagov.

Cytochrome oxidase (CCO), peroxidase, succinic dehydrogenase (SDG) and NADH-diaphorase were studied electron-cytochemically in leprous macrophages (LM) of granulomas of patients suffering from lepromatous leprosy. The LM peroxidase activity and location differed, this affecting the completeness of M. leprae phagocytosis. High CCO activity in LM cytoplasm was not a factor essentially influencing M. leprae disintegration. SDG and NADH-diaphorase, locating predominantly in membraneous structures of M. leprae, show low activity in LM cytoplasm.

[Histochemical study of reverse reactions in experimental leprosy in armadillos]. / Gistokhimicheskoe izuchenie reversivnykh reaktsii pri éksperimental'noi lepre u bronenostsev.

Morphological and histochemical characteristics of reverse reactions in M. leprae-infected armadillos are reviewed. The reverse reactions develop in generalized lepromatous disease and are characterized by a dramatic decrease in mycobacterial macrophage load and the appearance of lymphocytes, epithelioid and giant multinuclear cells with peripheral nucleus distribution. Histochemical investigation has shown a decrease in the activity of redox enzymes and alpha-naphthyl acetate esterase and an increase in beta-glucuronidase activity. The reverse reactions in the liver are accompanied by hepatic granuloma and hepatocyte destruction.

[Diagnostic test systems based on the immunoenzyme method in leprosy]. / Diagnosticheskie test-sistemy na osnove immunofermentnogo metoda pri lepre.

Diagnostic test systems for the detection of IgG and IgM to Mycobacterium leprae in the blood sera of leprosy patients and armadillos experimentally infected with M. leprae have been developed on the basis of the indirect immunoperoxidase assay. The possibility has been shown of prognosing the activity of the leprotic process in leprosy patients and the results of the experimental infection of armadillos by the dynamic increase of antibody reactions with the development of the infection.

[Pathomorphologic changes in the internal organs of intact and Mycobacterium leprae-infected 9-banded armadillos]. / Patomorfologicheskie izmeneniia vnutrennikh organov intaktnykh i zarazhennykh mikobakteriiami lepry deviatipoiasnykh bronenostsev.

The internal organs of nine-banded armadillos were examined histologically before and after inoculation of the animals with M. leprae. 3--4 months after the inoculation two animals developed tuberculoid structures in the lungs, liver and skin. A conclusion is made that experimental leprosy infection in nine-banded armadillos may run its course not only in the lepromatous but also in the tuberculoid form of the disease.