Vaccination of mice against Mycobacterium leprae infection

Singh, Nidhi; Lowe, Ann; Rees, R. J. W.; Colston, M. J.

doi:10.1128/iai.57.2.653-655.1989

Cited by 22 publications

(9 citation statements)

References 7 publications

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“…This hypothesis is supported by the ®nding that live bacilli induce higher levels of antituberculous resistance in experimental animals than either whole dead bacilli, or their cell components even when presented in a suitable adjuvant [31]. The girradiated whole cell vaccine of M. habana was found to provide protection against M. leprae and M. tuberculosis infections [18,21,32] in animal models. We carried out a preliminary search to evaluate the protective ef®cacy of the`excretory secretory' proteins isolated from the culture ®ltrate of multiplying mycobacteria (M. habana) and to identify the potential mechanisms involved in the generation of an effective immune response against M. tuberculosis infection in vaccinated animals.…”

Section: Discussionmentioning

confidence: 99%

“…We carried out a preliminary search to evaluate the protective ef®cacy of the`excretory secretory' proteins isolated from the culture ®ltrate of multiplying mycobacteria (M. habana) and to identify the potential mechanisms involved in the generation of an effective immune response against M. tuberculosis infection in vaccinated animals. We considered the M. habana whole cell vaccine as the positive control as it could provide better protection against tuberculosis as well as leprosy infections in experimental animals [18,21,32].…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms Involved in Protective Immune Response Generated by Secretory Proteins of Mycobacterium habana Against Experimental Tuberculosis

2000

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Live mycobacteria secrete a number of unique proteins early in their multiplication which are important for both the pathogenesis and the stimulation of speci®c host responses. We have investigated the mechanisms by which the host mounts immune response against tuberculosis after vaccination with secretory proteins (SP) of a vaccine candidate Mycobacterium habana TMC 5135. Mice vaccinated with SP of 10th day growth of M. habana, either alone or emulsi®ed in Freund's incomplete adjuvant (FIA) possessed antituberculous resistance and cellular immune responses against M. tuberculosis H 37 Rv. These proteins induced a signi®cant cutaneous delayed type hypersensitivity response in guinea pigs vaccinated with heat killed M. tuberculosis H 37 Rv, which was equivalent to that observed with a standard puri®ed protein derivative (PPD). The splenocytes of these guinea pigs have shown higher proliferative response after stimulation with SP than with PPD. The SP FIA immunization has been found to exert maximum prophylactic effect by potentiating both the oxygen dependent arms and enzymatic activities of macrophages. Macrophages from mice vaccinated with SP of M. habana produced enhanced levels of interleukin(IL)-2, interleukin-12 and interferon(IFN)-g. The protective as well as cell mediated immune responses were upregulated in SP immunized animals when compared to whole cell (M. habana) vaccinated animals. SDS-PAGE of SP from M. habana showed the prominent bands of 60, 32, 31 and 30 kDa. Furthermore, the western analysis of SP with pulmonary tuberculosis patient's serum has revealed the presence of immunoreactive antigens of 36, 35, 33/32 kDa. Overall study demonstrated that the secretory antigens released by actively growing M. habana bacilli could activate different arms of effective immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanisms Involved in Protective Immune Response Generated by Secretory Proteins of Mycobacterium habana Against Experimental Tuberculosis

2000

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“…Self-limiting growth of M. leprae occurs in the foot-pad of the mouse [23]. Protection against M. leprae infection can be induced by prior vaccination with live or dead M. leprae, BCG [24] or M. habana [25]. Recently, immunization with cell wall preparations of M. leprae, including extractable cell wail proteins, resulted in significant inhibition of the growth of M. leprae and corresponding T cell reactivity [13].…”

Section: Discussionmentioning

confidence: 99%

Cellular immune response to the cell walls ofMycobacterium lepraein leprosy patients and healthy subjects exposed to leprosy

Roche

Neupane

Britton

1992

Clinical and Experimental Immunology

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SUMMARYCell walls of M. leprae coni\^{ of complex arrangements of carbohydrate, lipid. peptidoglycan and protein molecules. Recently, cxtractable proteins of a wide range of molecular weights were identified as components ofthe cell wall. We have examined the cellular immune responses of Nepali leprosy patients to a cell wall preparation of M. leprae enriched for these proteins. Strong lymphocyte proliferative responses to the antigens were present in halfof the paucibacillary leprosy patients and in the majority of healthy control subject

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“…The fact that this antigen is recognized by the T cells of BCG-vaccinated individuals, as well as patients with leprosy, does not necessarily detract from its potential efficacy as a leprosy vaccine. Indeed, recent evidence suggests that the protective antigens of mycobacteria are those which are shared by other mycobacterial species rather than species-specific antigens (35)(36)(37). Studies with a murine model of leprosy support this possibility, as immunization of mice with the MLP fraction protected them from subsequent infection with leprosy bacilli (9).…”

Section: Discussionmentioning

confidence: 99%

Identification of an immunostimulating protein from Mycobacterium leprae

et al. 1990

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Despite the recent identification of a number of Mycobacterium leprae proteins, the major immunogenic determinants of this organism remain obscure. We isolated from M. leprae a potent immunostimulatory preparation, designated the MLP fraction, which contains a major protein of 35 kilodaltons (kDa). This protein was precipitated by monoclonal antibody ML03-A,, which recognizes a 35-kDa protein of M. leprae, and by sera obtained from patients with lepromatous leprosy. Neither sera from healthy controls nor sera from patients with pulmonary tuberculosis recognized the 35-kDa protein, and only one of four serum samples from patients with borderline tuberculoid leprosy reacted with this protein. The MLP fraction stimulated T-cell proliferation in patients with leprosy whose T cells proliferate in response to whole M. leprae cells. Apparently, the T-cell epitope associated with MLP is also expressed on M. tuberculosis and M. bovis BCG, since patients with pulmonary tuberculosis and BCG-vaccinated individuals demonstrated significant responses to the MLP fraction. The 35-kDa M. leprae protein, purified to homogeneity in the laboratory of P. J. Brennan, stimulated T-cell proliferative responses in all MLP-responsive subjects. These findings suggest that the 35-kDa protein present in MLP is an immunostimulatory component of M. leprae. In addition to serving as a useful probe for study of the T-cell anergy associated with lepromatous disease, this protein may ultimately be useful as a component of a vaccine designed to provide protection against infection with M. leprae. * Corresponding author. MATERIALS AND METHODSPatients. Heparinized blood was obtained from 11 patients with LL and 12 patients with borderline tuberculoid leprosy (BTL). The disease stage was classified by T. H. Rea of the Division of Dermatology, University of Southern California, as described by Ridley and Jopling (32). These patients were under treatment with dapsone or a combination of dapsone, rifampin, and clofazimine. None were receiving corticosteroids or thalidomide or had erythema nodosum leprosum when blood samples were taken. All of these patients had been previously studied for the ability of their T cells to proliferate in response to M. leprae in vitro (Mohagheghpour et al., unpublished data). Five of the patients with LL were included in this study because their T-cell responses to M. leprae were normal while the remaining patients with LL were nonresponders to M. leprae. Blood samples were also obtained from 7 patients with pulmonary tuberculosis (PT) from the Curicica Sanitarium, Rio de Janeiro, Brazil; 10 healthy volunteers who had received M. bovis BCG vaccinations; and 8 healthy individuals who had not been vaccinated with BCG.Antigens. Armadillo-derived whole M. leprae cells, lyophilized uninfected armadillo liver, and a 35-kDa M. Ieprae protein purified to homogeneity (single silver-stained band by sodium dodecyl sulfate [SDS]-polyacrylamide gel electrophoresis [PAGE]) were kindly provided by Collins. Recombinant M. leprae proteins ...

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Vaccination of mice against Mycobacterium leprae infection

Cited by 22 publications

References 7 publications

Mechanisms Involved in Protective Immune Response Generated by Secretory Proteins of Mycobacterium habana Against Experimental Tuberculosis

Mechanisms Involved in Protective Immune Response Generated by Secretory Proteins of Mycobacterium habana Against Experimental Tuberculosis

Cellular immune response to the cell walls ofMycobacterium lepraein leprosy patients and healthy subjects exposed to leprosy

Identification of an immunostimulating protein from Mycobacterium leprae

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