New use of BCG for recombinant vaccines

Stover, C. Kendall; Cruz, V F de la; Fuerst, Thomas R.; Burlein, Jeanne E.; Benson, Lina; Bennett, Linda; Bansal, Gulshan; Young, J F; Lee, Mong Hong; Hatfull, Graham F.; Snapper, Scott B.; Barletta, Raúl G.; Jacobs, William R.; Bloom, Barry R.

doi:10.1038/351456a0

Cited by 1,399 publications

(1,026 citation statements)

References 28 publications

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“…However, LM-OVA induced more numbers of annexin V ϩ OVA-specific CD8 ϩ T cells than those induced by BCG-OVA. Although it is not clear whether all annexin V ϩ CD8 ϩ T cells die, it is, however, quite possible that some level of apoptosis might be occurring during BCG-OVA infection, particularly during the peak effector phase (ϳdays [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Indeed, as is evident in Fig.…”

Section: Discussionmentioning

confidence: 94%

“…BCG-OVA is a previously described recombinant strain (19) engineered with a partial sequence of the OVA gene (codons 230 -359), downstream of the Ag 85B secretion signal (20), under the control of heat shock protein Laboratory of Cellular Immunology, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada 60 promoter (21). Codons 230 -359 of OVA gene encode the SIINFEKL epitope (OVA [257][258][259][260][261][262][263][264] ) and its flanking sequences (22).…”

Section: Bacterial Strainsmentioning

confidence: 99%

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Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Faassen

Saldanha

Gilbertson

et al. 2005

The Journal of Immunology

105

101

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During infection with lymphocytic choriomeningitis virus, CD8+ T cells differentiate rapidly into effectors (CD62LlowCD44high) that differentiate further into the central memory phenotype (CD62LhighCD44high) gradually. To evaluate whether this CD8+ T cell differentiation program operates in all infection models, we evaluated CD8+ T cell differentiation during infection of mice with recombinant intracellular bacteria, Listeria monocytogenes (LM) and Mycobacterium bovis (BCG), expressing OVA. We report that CD8+ T cells primed during infection with the attenuated pathogen BCG-OVA differentiated primarily into the central subset that correlated to reduced attrition of the primed cells subsequently. CD8+ T cells induced by LM-OVA also differentiated into central phenotype cells first, but the cells rapidly converted into effectors in contrast to BCG-OVA. Memory CD8+ T cells induced by both LM-OVA as well as BCG-OVA were functional in that they produced cytokines and proliferated extensively in response to antigenic stimulation after adoptive transfer. During LM-OVA infection, if CD8+ T cells were guided to compete for access to APCs, then they received reduced stimulation that was associated with increased differentiation into the central subset and reduced attrition subsequently. Similar effect was observed when CD8+ T cells encountered APCs selectively during the waning phase of LM-OVA infection. Taken together, our results indicate that the potency of the pathogen can influence the differentiation and fate of CD8+ T cells enormously, and the extent of attrition of primed CD8+ T cells correlates inversely to the early differentiation of CD8+ T cells primarily into the central CD8+ T cell subset.

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Section: Discussionmentioning

confidence: 94%

Section: Bacterial Strainsmentioning

confidence: 99%

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Faassen

Saldanha

Gilbertson

et al. 2005

The Journal of Immunology

105

101

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“…BCG Pasteur transformed with empty vector pMV261 was used as the control vaccine [37]. BCG strains and M. tuberculosis H37Rv (ATCC 27294) were propagated in Middlebrook 7H9 media supplemented with 10% albumin-dextrose-catalase enrichment (Difco Laboratories) or enumerated on oleic acid-albumin-dextrose-catalaseenriched Middlebrook 7H11 agar.…”

Section: Bacterial Culturementioning

confidence: 99%

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

et al. 2009

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The rational design of new vaccines engineered to target key components of the host immune response is crucial to aid control of important infectious diseases such as tuberculosis. In this report, we determined whether modifying the function of pulmonary APC could improve protection against infection with Mycobacterium tuberculosis. Targeted delivery to the lung of the cytokine GM‐CSF, expressed by the Mycobacterium bovis BCG vaccine strain, increased pulmonary DC numbers and secretion of the immunoregulatory cytokine IL‐12, compared with parental BCG immunization. This impact on APC number by BCG:GM‐CSF resulted in accelerated priming of antigen‐specific CD4+ T cells in the mediastinal lymph nodes and increased migration of activated CD4+ T cells into the lung. i.n. administration of BCG:GM‐CSF resulted in significantly increased protection against M. tuberculosis infection compared with mice vaccinated with BCG alone. BCG:GM‐CSF exhibited an improved safety profile, as immunodeficient RAG1−/− mice vaccinated i.n. with BCG:GM‐CSF survived significantly longer than control BCG‐vaccinated mice. These data demonstrate that manipulating immune cells in the lung by BCG‐based delivery of GM‐CSF can assist the development of protective mucosal immunity against pulmonary bacterial infection.

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“…The 1693 bp PCR-amplified DNA fragment was first cloned into a TA cloning vector (pDK101) and was subsequently moved into the ScaI site of pGOAL19, to generate the knockout construct pAZI0235. In order to convert pMV261 (Stover et al, 1991) into an integrating vector, a MluI-XbaI fragment from pYUB178 (Pascopella et al, 1994) containing att and int sites was used to replace a MluI-XbaI fragment (encompassing oriM) from pMV261. The resulting plasmid was designated pAZI272.…”

Section: Methodsmentioning

confidence: 99%

Inactivation of the ilvB1 gene in Mycobacterium tuberculosis leads to branched-chain amino acid auxotrophy and attenuation of virulence in mice

et al. 2009

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Acetohydroxyacid synthase (AHAS) is the first enzyme in the branched-chain amino acid biosynthesis pathway in bacteria. Bioinformatics analysis revealed that the Mycobacterium tuberculosis genome contains four genes (ilvB1, ilvB2, ilvG and ilvX) coding for the large catalytic subunit of AHAS, whereas only one gene (ilvN or ilvH) coding for the smaller regulatory subunit of this enzyme was found. In order to understand the physiological role of AHAS in survival of the organism in vitro and in vivo, we inactivated the ilvB1 gene of M. tuberculosis. The mutant strain was found to be auxotrophic for all of the three branched-chain amino acids (isoleucine, leucine and valine), when grown with either C 6 or C 2 carbon sources, suggesting that the ilvB1 gene product is the major AHAS in M. tuberculosis. Depletion of these branched chain amino acids in the medium led to loss of viability of the DilvB1 strain in vitro, resulting in a 4-log reduction in colony-forming units after 10 days. Survival kinetics of the mutant strain cultured in macrophages maintained with sub-optimal concentrations of the branched-chain amino acids did not show any loss of viability, indicating either that the intracellular environment was rich in these amino acids or that the other AHAS catalytic subunits were functional under these conditions. Furthermore, the growth kinetics of the DilvB1 strain in mice indicated that although this mutant strain showed defective growth in vivo, it could persist in the infected mice for a long time, and therefore could be a potential vaccine candidate.

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New use of BCG for recombinant vaccines

Cited by 1,399 publications

References 28 publications

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Reducing the Stimulation of CD8+ T Cells during Infection with Intracellular Bacteria Promotes Differentiation Primarily into a Central (CD62LhighCD44high) Subset

Modulation of pulmonary DC function by vaccine‐encoded GM‐CSF enhances protective immunity against Mycobacterium tuberculosis infection

Inactivation of the ilvB1 gene in Mycobacterium tuberculosis leads to branched-chain amino acid auxotrophy and attenuation of virulence in mice

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