Recombinant Mycobacterium bovis BCG

Bastos, Reginaldo G.; Borsuk, Sibele; Seixas, Fabiana Kömmling; Dellagostin, Odir A.

doi:10.1016/j.vaccine.2009.08.044

Cited by 75 publications

(72 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since the first transformation of mycobacteria with foreign DNA, the recombinant BCG technology has been used to evaluate the expression of foreign protec- [36]. Although the expression of DT antigens in different bacterial species has been previously done [8] [37]- [41], in BCG the expressed DT antigens came from the mutant CRM 197 [27] and the diphtheria toxin dtb gene of the PW8 vaccine strain [42].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium bovis BCG as a Delivery System for the dtb Gene Antigen from Diphtheria Toxin

Nascimento¹,

Dellagostin²,

Matos³

et al. 2017

AJMB

Self Cite

View full text Add to dashboard Cite

Diphtheria is a fulminant bacterial disease caused by toxigenic strains of Corynebacterium diphtheriae whose local and systemic manifestations are due to the action of the diphtheria toxin (DT). The vaccine which is used to prevent diphtheria worldwide is a toxoid obtained by detoxifying DT. Although associated with high efficacy in the prevention of disease, the current anti-diphtheria vaccine, one of the components of DTP (diphtheria, tetanus and pertussis triple vaccine), may present post vaccination effects such as toxicity and reactogenicity resulting from the presence of contaminants in the vaccine that originated during the process of production and/or detoxification. Therefore, strategies to develop a less toxic and at the same time economically viable vaccine alternatives are needed to improve existing vaccines in use worldwide. In this study, the Moreau substrain of BCG which is used in Brazil as a live vaccine against human tuberculosis was genetically modified to carry and express the gene encoding for the diphtheria toxin fragment B (DTB). As such, the DNA sequence encoding the dtb gene was cloned into the pUS977 shuttle vector for cytoplasmic expression and successfully introduced into BCG cells by electroporation. Mice immunized with recombinant BCG expressing DTB showed seroconversion with the detection of specific antibodies against DTB. Also, rBCGs stably expressing DTB persisted up to 60 days in the absence of selective pressure in mice and cell viability did not change significantly during the period tested. Finally, immune sera from BALB/c mice vaccinated with rBCGpUS977dtb PW8 were preliminarily tested for their capacity of neutralizing the diphtheria toxin in the Vero Cells assay.How to cite this paper: Nascimento, D.V.,

show abstract

Section: Discussionmentioning

confidence: 99%

Mycobacterium bovis BCG as a Delivery System for the dtb Gene Antigen from Diphtheria Toxin

Nascimento¹,

Dellagostin²,

Matos³

et al. 2017

AJMB

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, technological advancements in the genomics of mycobacteria have improved our understanding of the biology of this slow-growing pathogen and have helped the conception of strategies to evaluate BCG as a vaccine delivery vector [57]. Consequently, antigens of bacteria, parasites, and viruses have been expressed in BCG and it has been shown that recombinant BCG (rBCG) elicits both cellular and humoral immune responses against heterologous antigens [54][55][56]. However, it was only in recent years that rBCG has attracted more attention as consequences stimulated by initiatives to develop new vaccines against TB.…”

Section: Gene Vectorsmentioning

confidence: 99%

“…However, it was only in recent years that rBCG has attracted more attention as consequences stimulated by initiatives to develop new vaccines against TB. It has been demonstrated that rBCG over expressing antigens of M. tuberculosis is more efficient in conferring protection against tuberculosis than the wild type BCG strain [55].…”

Section: Gene Vectorsmentioning

confidence: 99%

Vaccine Against Entheropathogenic E. colii: A Systematic Review

Vasconcellos¹,

Silva²,

Nascimento³

et al. 2017

IJVR

View full text Add to dashboard Cite

Enteric diseases are a major cause of childhood death in the developing world, ranking as the second cause of death in children. Enteropathogenic Escherichia coli(EPEC) are important diarrheal pathogens of children under 5 years of age. Due to high mortality, several international organizations such as the WHO and UNICEF have dedicated preventive and control programs for diarrheal diseases. Among the suggested initiatives aiming to prevent infectious diarrhea include vaccine development and improvement in sanitation and water and food supplies.Upon contact with host cells, EPEC delivers an array of virulence protein factors, which integrated actions interferes with the normal adjusting the targets molecular cell functions leading to diarrhea. The locus of entherocyte effacement (LEE)pathogenicity island contains genes encoding synthesis of the EPEC virulence factors membrane adhesin intimin, T3SS (Esc and Sep proteins), chaperones (Ces proteins), translocators (EspA, EspB, and EspD), effector proteins (EspF, EspG, EspH, Map and EspZ), the translocated intimin receptor (Tir), and the regulatory protein Ler (LEEencoded regulator).Bundle-forming pilus (BfpA) is another virulence factor that mediates the initial contact between EPEC and the host cell. BfpA is encoded by a gene localized on a 50-70 MDa plasmid and is designated as EPEC adherence factor (EAF). BfpA, intimin and translocated Tir initiate EPEC infection. This repertoire of virulence factors offers strategic epitopes as vaccine candidates.Employing the proposed technologies for modern vaccines, recombinant Mycobacterium smegmatis (Smeg) and Mycobacterium bovis BCG strains were constructed to express BfpA, intimin and EspA. Recombinant clones were selected based on kanamycin resistance. Recombinant proteins are immunogenic, and the resultant antibodies recognize and block EPEC adhesion onto HEp-2 target cells. In attention to regulatory agency recommendations, kanamycin should not be used to produce rBCG expressing the E. coli EPEC virulence factors BfpA, intimin and EspA. Accordingly, an expression system with a Pasteur auxotrophic BCG mutant for leucine (BCG Pasteur ΔleuD) and a replicative vector (pUP410)should be used. Obtained recombinants will be grown in large scale, and their immunogenic effectivity and human safety submitted to WHO indicated quality controls.

show abstract

“…The current vaccine, bacillus CalmetteGuérin (BCG), is a living, attenuated strain (actually several different strains) of Mycobacterium bovis, which has served as a model for new TB vaccines and a gold standard for their evaluation in animal models [8]. BCG has many characteristics that recommend it as a platform for new TB vaccines, and several of the promising new vaccines utilize recombinant BCG strains overexpressing the genes for several mycobacterial antigens [9,10]. However, the fact that BCG does not seem to protect against adult pulmonary TB in some high-burden settings has stimulated the search for other types of TB vaccines.…”

Section: Variety Is the Spice Of Lifementioning

confidence: 99%

TB vaccines: the paradigms they are a-shifting

McMurray

2009

Expert Review of Vaccines

View full text Add to dashboard Cite

"The urgency to license a new TB vaccine has driven a worldwide effort over the past 20 years involving basic scientists, public and private funding agencies, regulatory bodies, and disease control experts in high-burden countries."Traditional roadblocks to effective TB control (e.g., lack of attention to the disease, lack of resources, antiquated diagnostic tests, lack of patient compliance with therapy and a huge reservoir of persistently infected individuals) have been compounded by the terrible synergy between TB and HIV, and the development of almost untreatable multi-and extensively drug-resistant strains of Mycobacterium tuberculosis [1]. Case-finding and chemotherapy employing the Directly Observed Treatment, Short-course strategy, and several promising new TB drugs currently in the pipeline, will undoubtedly continue to have a significant impact on TB incidence [2,3]. However, it is clear that an effective vaccine is essential if TB is to be controlled as rapidly as possible [4][5][6]. The urgency to license a new TB vaccine has driven a worldwide effort over the past 20 years involving basic scientists, public and private funding agencies, regulatory bodies, and disease control experts in highburden countries [7]. That effort has been shaped at various stages by several paradigms that reflected the current understanding of the type of vaccine that would be needed, the manner in which vaccines should be evaluated for efficacy in animal models, the process by which preclinical development of vaccines would occur, the design of clinical trials, and the public and private organizations that would participate in the process. Almost without exception, those paradigms have shifted as the understanding of vaccine-induced protection has improved, an appreciation for the biological relevance of certain animal models of TB has grown, new strategies for organizing and funding preclinical development and human trials have emerged, and the realities of testing and using TB vaccines in diverse high-burden populations have become apparent. Variety is the spice of lifeIn general, the induction of protective cell-mediated immunity is much more challenging than inducing a protective antibody response, a fact which has complicated the search for a better TB vaccine. The current vaccine, bacillus CalmetteGuérin (BCG), is a living, attenuated strain (actually several different strains) of Mycobacterium bovis, which has served as a model for new TB vaccines and a gold standard for their evaluation in animal models [8]. BCG has many characteristics that recommend it as a platform for new TB vaccines, and several of the promising new vaccines utilize recombinant BCG strains overexpressing the genes for several mycobacterial antigens [9,10]. However, the fact that BCG does not seem to protect against adult pulmonary TB in some high-burden settings has stimulated the search for other types of TB vaccines. The traditional approach of using purified components of the bacterium together with an effective adjuvant has been modernize...

show abstract

Recombinant Mycobacterium bovis BCG

Cited by 75 publications

References 118 publications

<i>Mycobacterium bovis</i> BCG as a Delivery System for the <i>dtb</i> Gene Antigen from Diphtheria Toxin

<i>Mycobacterium bovis</i> BCG as a Delivery System for the <i>dtb</i> Gene Antigen from Diphtheria Toxin

Vaccine Against Entheropathogenic E. colii: A Systematic Review

TB vaccines: the paradigms they are a-shifting

Contact Info

Product

Resources

About

Recombinant Mycobacterium bovis BCG

Cited by 75 publications

References 118 publications

&lt;i&gt;Mycobacterium bovis&lt;/i&gt; BCG as a Delivery System for the &lt;i&gt;dtb&lt;/i&gt; Gene Antigen from Diphtheria Toxin

&lt;i&gt;Mycobacterium bovis&lt;/i&gt; BCG as a Delivery System for the &lt;i&gt;dtb&lt;/i&gt; Gene Antigen from Diphtheria Toxin

Vaccine Against Entheropathogenic E. colii: A Systematic Review

TB vaccines: the paradigms they are a-shifting

Contact Info

Product

Resources

About

<i>Mycobacterium bovis</i> BCG as a Delivery System for the <i>dtb</i> Gene Antigen from Diphtheria Toxin

<i>Mycobacterium bovis</i> BCG as a Delivery System for the <i>dtb</i> Gene Antigen from Diphtheria Toxin