Immune responses induced by recombinant BCG strains according to level of production of a foreign antigen: MalE

Himmelrich, Hayo; Lo‐Man, Richard; Winter, Nathalie; Guermonprez, Pierre; Sedlik, Christine; Rojas, Marie; Monnaie, Didier; Gheorghiu, M; Lagranderie, M.; Hofnung, Maurice; Gicquel, Brigitte; Clément, Jean-Marie; Leclerc, Claude

doi:10.1016/s0264-410x(00)00070-0

Cited by 29 publications

(19 citation statements)

References 30 publications

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“…One possible reason for the lack of presentation of antigen from M. smegmatis in BMDC and splenic dendritic cells appears to be that no detectable secretion of OVApet is observed by ELISA compared to that from M. bovis BCG, as secreted antigen from mycobacteria has been shown to be the most immunogenic form (18,21). However, it cannot be ruled out that M. smegmatis may upregulate its secretion of OVApet after uptake by dendritic cells, particularly by DC2.4 cells.…”

Section: Discussionmentioning

confidence: 99%

Closely Related Mycobacterial Strains Demonstrate Contrasting Levels of Efficacy as Antitumor Vaccines and Are Processed for Major Histocompatibility Complex Class I Presentation by Multiple Routes in Dendritic Cells

Cheadle¹,

O'Donnell

Selby³

et al. 2005

Infect Immun

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Mycobacterium bovis BCG, the only vaccine available against tuberculosis (22), has also been used successfully as a vaccine against leprosy (29) and, for over 20 years, as a local immunotherapy against superficial bladder cancer (2). Mycobacterium smegmatis is a related organism which has potential advantages as a recombinant vaccine over M. bovis BCG, as it is nonpathogenic and frequently commensal in humans (36, 42). Indeed, emulsified M. smegmatis and M. bovis BCG have comparable antitumor activity in a tumor immunotherapy model (56). The recent realization that mycobacteria are promising vehicles for a new generation of recombinant vaccines lends urgency to investigating the relative value of different strains in that role.Despite their close relationship, there are several key differences between M. bovis BCG and M. smegmatis. M. bovis BCG is derived from the intracellular pathogen M. bovis and survives in host cells for months (31). In contrast, M. smegmatis is rapidly destroyed within infected cells and is nonpathogenic. Highly pathogenic mycobacteria such as M. tuberculosis can survive and replicate within cells because they inhibit phagosome maturation and hence their own degradation (11). Although the exact mechanism is not yet fully understood (47), it is known that such mycobacteria prevent acidification of the phagosome (13) and subsequent formation of a phagolysosome. M. bovis BCG shares many characteristics with M. tuberculosis and induces biochemical markers of maturation arrest (53, 54). On the other hand, M. smegmatis does not arrest phagosome maturation and is degraded rapidly by phagolysosomal proteases, which probably accounts for its lack of pathogenicity (28,54).Since the development of mycobacterium-Escherichia coli shuttle plasmids (23), there has been much interest in the generation of recombinant mycobacteria as vaccines against infectious disease, such as tuberculosis and human immunodeficiency virus. Furthermore, a recent study has also shown that recombinant M. bovis BCG can also protect against tumor challenge in model systems (15). The authors demonstrated that if they vaccinated mice with 10 2 or 10 4 M. bovis BCG secreting OVA and then challenged at day 30, 120, or 150 with B16-OVA, a significant delay in tumor growth was observed.It is generally accepted that the generation of effective antitumor and anti-infective immune responses requires antigenpresenting cells to prime cytotoxic T lymphocytes and T-helper cells by processing antigen and presenting it on MHC class I and class II molecules, respectively. Mice immunized with recombinant M. bovis BCG expressing human immunodeficiency virus antigens (1) and ␤-galactosidase (49) generate specific cytotoxic T lymphocytes, but the mechanisms underlying anti-* Corresponding author. Present address:

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Section: Discussionmentioning

confidence: 99%

Closely Related Mycobacterial Strains Demonstrate Contrasting Levels of Efficacy as Antitumor Vaccines and Are Processed for Major Histocompatibility Complex Class I Presentation by Multiple Routes in Dendritic Cells

Cheadle¹,

O'Donnell

Selby³

et al. 2005

Infect Immun

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“…The marked differences noted for the two types of recombinant vaccines based on Sm14, in terms of the ability to stimulate humoral immunity, were not entirely unexpected given that they would be processed by and presented to the immune system by different mechanisms. In this context, it should be noted that the subcellular location of the recombinant antigen has been reported to influence both the quantity and quality of the immune response to a number of antigens produced by rBCG (15,17,29). Yet there are numerous examples of rBCG-based vaccines which are capable of inducing strong humoral immune responses to a variety of antigens (25).…”

Section: Discussionmentioning

confidence: 99%

“…Several advantages are associated with the use of BCG as an antigen-presenting system, including its known adjuvant properties, its ability to elicit humoral or cellular immune responses toward heterologous antigens, its thermostability, which eliminates the need for a cold chain, and most importantly, the possibility of obtaining an efficient immune response by using a single dose. During the last 10 years, expression systems have been developed for the production of a variety of bacterial, parasitic, and viral antigens by BCG, and the capacity of these recombinant systems to induce both cellular and humoral im-mune responses in various experimental models is well documented (2,17,20,25). Furthermore, it has been demonstrated that recombinant BCG strains can induce protective immunity in animal models (1,24,29).…”

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confidence: 99%

RecombinantMycobacterium bovisBCG Expressing the Sm14 Antigen ofSchistosoma mansoniProtects Mice from Cercarial Challenge

et al. 2004

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The Sm14 antigen of Schistosoma mansoni was cloned and expressed in Mycobacterium bovis BCG as a fusion with the Mycobacterium fortuitum ␤-lactamase protein under the control of its promoter, pBlaF*; the protein was localized in the bacterial cell wall. The rBCG-Sm14 strain was shown to be relatively stable in cultured murine and bovine monocytes in terms of infectivity, bacterial persistence, and plasmid stability. The immunization of mice with rBCG-Sm14 showed no induction of anti-Sm14 antibodies; however, splenocytes of immunized mice released increased levels of gamma interferon upon stimulation with recombinant Sm14 (rSm14), indicating an induction of a Th1-predominant cellular response against Sm14. Mice immunized with one or two doses of rBCG-Sm14 and challenged with live S. mansoni cercaria showed a 48% reduction in worm burden, which was comparable to that obtained by immunization with three doses of rSm14 purified from Escherichia coli. The data presented here further enhance the status of Sm14 as a promising candidate antigen for the control of schistosomiasis and indicate that a one-dose regimen of rBCG-Sm14 could be considered a convenient means to overcome many of the practical problems associated with the successful implementation of a multiple-dose vaccine schedule in developing countries.

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“…The construction and characterization of rBCG.MalE expressing the E. coli MalE gene (previously described as rBCG(p BlaF* -SS BlaF -SS malEmalE) have been reported previously (20). For immunization, BCG strains were first cultivated on Loewenstein-Jensen medium containing 20 g/ml kanamycin, and then transferred onto Sauton medium.…”

Section: Bacterial Strains and Culture Conditionsmentioning

confidence: 99%

“…Therefore, in the present study we analyzed the kinetics of Th1 and Th2 responses directed against a defined mycobacterial Ag as well as against its epitopic determinants during the course of BCG infection using a recombinant BCG expressing a reporter Ag, the Escherichia coli MalE protein (9,20). The cytokine response specific for MalE was analyzed as well as the specific T cell responses to defined MHC class II-restricted MalE epitopes.…”

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confidence: 99%

The Shift of Th1 to Th2 Immunodominance Associated with the Chronicity ofMycobacterium bovisBacille Calmette-Guérin Infection Does Not Affect the Memory Response

Jiao

Lo‐Man²,

Winter

et al. 2003

The Journal of Immunology

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In the present study we investigated the shaping and evolution of the immunodominance of the T cell response during a chronic mycobacterial infection. Using a recombinant bacille Calmette-Guérin expressing a reporter Ag, the Escherichia coli MalE protein, we analyzed the peptide specificity and the cytokine profile of the T cell response to the reporter Ag by ELISPOT. During the early steps of infection, the T cell response was focused on two dominant MalE epitopes and was characterized by a pure IFN-γ response. Then, in the course of infection the initial IFN-γ response to these two epitopes shifted to a mixed IFN-γ/IL-4 response. At the same time, the peptide specificity of the T cell response was broadened to two additional MalE epitopes characterized by a unique IL-4 response resulting in the establishment of a dominant IL-4 response to the MalE protein at 16 wk postinfection. However, this phenomenon did not impair the outcome of a predominant IFN-γ response upon subsequent MalE recall in vivo performed in the presence of CFA, a Th1-driving adjuvant. These results indicate that the Th2 nature of the immune response established during a chronic infection, which most likely reflects regulatory mechanisms to allow the return to T cell homeostasis, does not shape the Th1/Th2 nature of the memory response.

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Immune responses induced by recombinant BCG strains according to level of production of a foreign antigen: MalE

Cited by 29 publications

References 30 publications

Closely Related Mycobacterial Strains Demonstrate Contrasting Levels of Efficacy as Antitumor Vaccines and Are Processed for Major Histocompatibility Complex Class I Presentation by Multiple Routes in Dendritic Cells

Closely Related Mycobacterial Strains Demonstrate Contrasting Levels of Efficacy as Antitumor Vaccines and Are Processed for Major Histocompatibility Complex Class I Presentation by Multiple Routes in Dendritic Cells

RecombinantMycobacterium bovisBCG Expressing the Sm14 Antigen ofSchistosoma mansoniProtects Mice from Cercarial Challenge

The Shift of Th1 to Th2 Immunodominance Associated with the Chronicity ofMycobacterium bovisBacille Calmette-Guérin Infection Does Not Affect the Memory Response

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