Expanding the antigenic repertoire of BCG improves protective efficacy against aerosol Mycobacterium tuberculosis infection

Palendira, Umaimainthan; Spratt, Joanne M.; Britton, Warwick J.; Triccas, James A.

doi:10.1016/j.vaccine.2004.10.007

Cited by 39 publications

(31 citation statements)

References 23 publications

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“…rBCG expressing the fusion protein of ESAT-6 and one member Ag85A complex, Ag85B, also did not improve the short-time protection efficacy against TB in a mouse model. 35,36 Meanwhile, DNA vaccine pE6/85B which consisted of ESAT-6 and Ag85B fusion gene with tpa signal sequence could provide the protection against M. tuberculosis infection in vaccinated mice and be used as an effective booster after BCG immunization, 16 which provided further evidence to support our conclusion. Moreover, there are some rBCG strains, such as rBCG30, 23 rBCG::AB, 24 rBCG::X, 37 rBCG::85B-Rv3425, 38 rBCG UreC: Hly, 28 and AERAS-rBCG, 39 etc, providing stronger and/or longer-lasting protective efficacy than BCG in animal models or in humans.…”

Section: Discussionsupporting

confidence: 62%

Comparison of BCG prime-DNA booster and rBCG regimens for protection against tuberculosis

Tan¹,

Teng³

et al. 2013

Human Vaccines & Immunotherapeutics

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Section: Discussionsupporting

confidence: 62%

Comparison of BCG prime-DNA booster and rBCG regimens for protection against tuberculosis

Tan¹,

Teng³

et al. 2013

Human Vaccines & Immunotherapeutics

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“…Consequently, although BCG is considered a safe vaccine and has been administered since 1921 to an estimated 3 billion people, it has proved insufficient to control the spread of TB (2). BCG is amenable to genetic manipulation, and overexpression of protective antigens in BCG can improve the efficacy of the vaccine in animal models of TB (9,20,23). An alternative approach is to express immunostimulatory molecules in BCG.…”

mentioning

confidence: 99%

Secretion of Functional Monocyte Chemotactic Protein 3 by RecombinantMycobacterium bovisBCG Attenuates Vaccine Virulence and Maintains Protective Efficacy againstM. tuberculosisInfection

et al. 2007

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A strain of Mycobacterium bovis BCG that secretes high levels of functional murine monocyte chemotactic protein 3 (BCG MCP-3 ) was developed. Mice vaccinated with BCG MCP-3 displayed increased lymphocyte migration in vivo and augmented antigen-specific T-cell responses compared to mice vaccinated with BCG alone. The level of protection afforded by BCG MCP-3 was equivalent to that with control BCG; however, immunodeficient mice infected with BCG MCP-3 survived significantly longer than mice infected with the control BCG strain. Therefore, BCG MCP-3 may be a safer alternative than conventional BCG for vaccination of immunocompromised individuals.Tuberculosis (TB) remains a leading cause of worldwide mortality alongside human immunodeficiency virus and malaria. Recent figures suggest that each year there are approximately 8 million new cases and 2 million deaths (17). The current vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is only partially effective against lung TB, the contagious form of the disease, with vaccine efficacy ranging from 0 to 80% (median of 50%) (7). Consequently, although BCG is considered a safe vaccine and has been administered since 1921 to an estimated 3 billion people, it has proved insufficient to control the spread of TB (2). BCG is amenable to genetic manipulation, and overexpression of protective antigens in BCG can improve the efficacy of the vaccine in animal models of TB (9,20,23). An alternative approach is to express immunostimulatory molecules in BCG. Murine cytokines, including interleukin-2, interleukin-18, gamma interferon (IFN-␥), and granulocyte-macrophage colony-stimulating factor, can be secreted by BCG in a functional form; however, the ability of these vaccines to protect against TB has not been tested (13,16,18). The monocyte chemotactic proteins (MCP) are a subset of the CC or ␤-chemokines consisting of four members, MCP-1, -2, -3, and -4 (with MCP-5 in the mouse only), which are induced by viral and bacterial infections in many cell types (26, 31). MCP-3 is a pleiotropic chemokine that binds the receptors CCR1, CCR2, and CCR3 (15). These receptors are expressed on mononuclear phagocytes, T cells, B cells, natural killer cells, basophils, eosinophils, neutrophils, and particularly immature dendritic cells (1,3,11,26,32). MCP-3 is highly expressed by macrophages exposed to mycobacterial components or M. tuberculosis-infected mice (27, 30). Mice lacking CCR2 were acutely susceptible to M. tuberculosis infection and exhibited a significant reduction in early macrophage recruitment and a later defect in dendritic cell and T-cell migration (22). These results clearly demonstrate that chemokines, such as MCP-3, are vital in the response to M. tuberculosis infection, as they are required for the selective migration of the cells essential for the generation of a protective immune response.In this report, we demonstrate that murine MCP-3 (mMCP-3) can be expressed and secreted by BCG in an active form. Secretion of MCP-3 markedly improved the immunogenicity of BCG a...

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“…Recombinant BCG strains offer a promising strategy for live vaccine development and encouraging results have been obtained using rBCG over-expressing important mycobacterial antigens (11,16,20). We demonstrate that addition of Ald to BCG does not influence protective efficacy; vaccination of mice with BCG:Ald provided a similar level of protection against aerosol M. tuberculosis infection as BCG harbouring control vector (Fig.…”

mentioning

confidence: 59%

“…Therefore although the introduction to BCG of the M. tuberculosis ald gene restores Ald activity, this does not alter the virulence of the vaccine strain. Protective efficacy of BCG:Ald against aerosol M. tuberculosis infection: The addition to BCG of M. tuberculosis of specific and shared antigens improves protective efficacy (11,16). Ald is a highly abundant secreted protein of M. tuberculosis that is absent from BCG, and the inability to catabolise alanine has been postulated to limit BCG efficacy (6).…”

mentioning

confidence: 99%

Contribution of L‐Alanine Dehydrogenase to In Vivo Persistence and Protective Efficacy of the BCG Vaccine

Scandurra

Ryan

Pinto

et al. 2006

Microbiology and Immunology

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The tuberculosis (TB) vaccine strain Mycobacterium bovis BCG is unable to utilise alanine and this deficiency is thought to inhibit the growth of the vaccine in vivo and limit vaccine efficacy. In this report we demonstrate that L‐alanine catabolism can be conferred on BCG by introduction of the gene encoding L‐alanine dehydrogenase (Ald) of Mycobacterium tuberculosis. Restoration of Ald activity did not change the in vivo growth of BCG in macrophages or mice, and protection against aerosol M. tuberculosis infection was not altered by addition of ald to the BCG vaccine. These results demonstrate that the inability to utilise L‐alanine is not a contributing factor to the attenuated phenotype of BCG and does not influence the protective efficacy of the vaccine against TB.

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Expanding the antigenic repertoire of BCG improves protective efficacy against aerosol Mycobacterium tuberculosis infection

Cited by 39 publications

References 23 publications

Comparison of BCG prime-DNA booster and rBCG regimens for protection against tuberculosis

Comparison of BCG prime-DNA booster and rBCG regimens for protection against tuberculosis

Secretion of Functional Monocyte Chemotactic Protein 3 by RecombinantMycobacterium bovisBCG Attenuates Vaccine Virulence and Maintains Protective Efficacy againstM. tuberculosisInfection

Contribution of L‐Alanine Dehydrogenase to In Vivo Persistence and Protective Efficacy of the BCG Vaccine

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