Growth of Two Strains of Mycobacterium bovis (BCG) in Athymic Mice

Takeya, Kenji; Nomoto, Kikuo; Muraoka, Susumu; Shimotori, Shoichi; Taniguchi, Toru; Miyake, Tsunenori

doi:10.1099/00221287-100-2-403

Cited by 11 publications

(3 citation statements)

References 2 publications

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“…Therefore, the results support the interpretation that CD4 + T cells are not needed for stabilization of BCG infection in the liver, spleen, and kidneys after 2-3 wk of progressive BCG growth. These results with nude mice are in agreement with growth curves published some years ago by others, which on examination show that nude mice (19,20) and neonatally thymectomized mice (17), although incapable of resolving infection, were capable of restricting BCG growth to a considerable extent in their livers and spleen after a certain stage of infection. The results presented here showing that SCID mice engrafted with lymph node cells depleted of CD4 + T cells are capable of expressing a substantial level of anti-BCG resistance support this conclusion.…”

Section: -1'-i Ve Spl E Isupporting

confidence: 92%

Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.

Izzo

North

1992

The Journal of Experimental Medicine

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SummaryDepleting thymectomized mice of CD4 + T cells, or CD4 + plus CD8 + T cells, rendered them incapable of resolving Bacillus-Calmette-Guerin (BCG) infection in their livers, spleens, kidneys, and lungs. However, it did not render them incapable of stabilizing infection in the latter three organs after an initial period of BCG growth. Athymic nude mice showed a similar capacity to control BCG growth in these organs after a certain stage of infection. In contrast, congenitally severe combined immunodeficient (SCID) mice appeared to offer no resistance to BCG infection, in that the organism grew progressively in all organs of these mice and was lethal for them beginning on day 55 of infection. The results suggest that, although CD4 + T cells are important for resolving BCG infection, an odB T cell-independent mechanism of resistance can be acquired at 2-3 wk of infection that is capable of inhibiting further BCG growth in all organs except the lungs. Because this mechanism is absent from SCID mice, it is likely that it depends on the functions of 3~/~ T cells, B cells, or both types of cells. In keeping with this possibility is the additional finding that SCID mice engrafted with lymph node cells depleted of CD4 + or CD8 + T cells were capable of expressing an appreciable level of resistance against BCG infection.I t is generally believed, on the basis of results obtained from adoptive immunization and T cell depletion studies, that immunity to infection with mycobacteria is mediated by T cells. It has been known for some time, for example, that mice in the process of resolving BCG infection acquire T cells that are capable, on passive transfer, of conferring increased antimycobacterial resistance on naive recipient mice (1, 2). More recently, experiments with mice depleted of T cell subsets have shown that depletion of CD4 + T cells, but not of CD8 + T cells, results in a reduced capacity to resolve BCG infection (3) and to defend against infection with Mycobacteriura tuberculosis (4). However, in the case of BCG infection, the same T cell depletion studies (3) revealed that the absence of CD4 + , or both T cell subsets, did not leave mice completely defensdess against infection. On the contrary, mice so depleted showed a surprising capacity to halt progressive growth of BCG after a certain stage of infection. Therefore, the interpretation that CD4 + T ceils are pivotal for resistance to BCG infection is not supported by the evidence. This paper will show that mice depleted of CD4 + plus CD8 + T ceils, and athymic nude mice, can acquire the ability to stabilize BCG infection after 2-3 wk of BCG growth. It will show, in addition, that SCID mice permit progressive BCG growth in all organs and begin dying of infection from day 55 on, but not if they are engrafted with coisogenic lymph node cells depleted of CD4 + or CD8 + T ceils. Therefore, acquired resistance to BCG infection is partly dependent on a mechanism that is independent of CD4 + and CD8 + T cells. Materials and MethodsMice. B6D2FI (C57BL/6 x DBA/2) mi...

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Section: -1'-i Ve Spl E Isupporting

confidence: 92%

Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.

Izzo

North

1992

The Journal of Experimental Medicine

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“…In order to fully take advantage of the potential benefits of traditional live vectors in HIV-1 vaccine development, we studied the Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrain Tokyo 172 (6) and the replication-deficient vaccinia virus vaccine strain DIs (22,50), both of which have been shown to be nonpathogenic when inoculated into immunodeficient animals (41,51,53) as live recombinant vaccine vehicles (1,(17)(18)(19)(46)(47)(48). As further evidence of the potential of the live vectors for use in HIV/AIDS vaccines, we noted that a recombinant M. bovis BCG vector candidate vaccine for HIV-1-induced positive immune responses in animals (17,46).…”

mentioning

confidence: 99%

Priming-Boosting Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and a Nonreplicating Vaccinia Virus Recombinant Leads to Long-Lasting and Effective Immunity

Ami

Izumi

Matsuo

et al. 2005

J Virol

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Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-␥) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-␥ activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

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“…With respect to safety, traditional live vaccines, which have been administered safely to both the healthy and the HIV-infected individuals, may be the vectors of choice for HIV-1 vaccines. To fully take advantage of the benefits of such traditional vaccines in the development of anti-HIV vaccines, we studied BCG Tokyo 172 strain and the replication-deficient vaccinia vaccine strain DIs [55, 56] both of which have been shown to be nonpathogenic when inoculated into immune-deficient animals as live recombinant vaccine vehicles [57]. The vaccinia virus DIs have been tested clinically as a smallpox vaccine in Japanese infants and proved to be quite safe.…”

Section: Hiv/aids Vaccinementioning

confidence: 99%

Mycobacterium bovisBacille Calmette-Guérin as a Vaccine Vector for Global Infectious Disease Control

Matsuo

Yasutomi

2011

Tuberculosis Research and Treatment

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Mycobacterium bovis bacille Calmette-Guérin (BCG) is the only available vaccine for tuberculosis (TB). Although this vaccine is effective in controlling infantile TB, BCG-induced protective effects against pulmonary diseases in adults have not been clearly demonstrated. Recombinant BCG (rBCG) technology has been extensively applied to obtain more potent immunogenicity of this vaccine, and several candidate TB vaccines have currently reached human clinical trials. On the other hand, recent progress in the improvement of the BCG vector, such as the codon optimization strategy and combination with viral vector boost, allows us to utilize this bacterium in HIV vaccine development. In this paper, we review recent progress in rBCG-based vaccine studies that may have implications in the development of novel vaccines for controlling global infectious diseases in the near future.

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Growth of Two Strains of Mycobacterium bovis (BCG) in Athymic Mice

Cited by 11 publications

References 2 publications

Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.

Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.

Priming-Boosting Vaccination with Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and a Nonreplicating Vaccinia Virus Recombinant Leads to Long-Lasting and Effective Immunity

Mycobacterium bovisBacille Calmette-Guérin as a Vaccine Vector for Global Infectious Disease Control

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