Protection against<i>Mycobacterium avium</i>by DNA Vaccines Expressing Mycobacterial Antigens as Fusion Proteins with Green Fluorescent Protein

Velaz-Faircloth, Maria; Cobb, Alison J; Horstman, Amanda L.; Henry, Stanley C.; Frothingham, Richard

doi:10.1128/iai.67.8.4243-4250.1999

Cited by 38 publications

(9 citation statements)

References 44 publications

(52 reference statements)

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“…The 3-log 10 reduction in bacterial load in the spleen following immunization with DNA-Av35 and plasmid IL-12 was significantly higher than the level of protection observed in separate experiments with DNA vaccines expressing the M. avium 65 000 MW heat-shock protein or M. bovis antigen 85A. 11 These induced a four-and eightfold reduction in M. avium load in the spleen, respectively. 11 The apparent enhanced effect with DNA-Av35 and p2AIL12 may be due to both the immunodominance of the 35 000 MW protein and the adjuvant effect of IL-12.…”

Section: Discussionmentioning

confidence: 73%

“…11 These induced a four-and eightfold reduction in M. avium load in the spleen, respectively. 11 The apparent enhanced effect with DNA-Av35 and p2AIL12 may be due to both the immunodominance of the 35 000 MW protein and the adjuvant effect of IL-12.…”

Section: Discussionmentioning

confidence: 95%

“…3 Immunization with the vaccine strain M. bovis bacille Calmette-Guèrin (BCG) provides partial, but variable, protection against tuberculosis and leprosy 4 and new approaches to immunization against mycobacterial infections are urgently required. Recently a number of protein and DNA vaccines expressing single mycobacterial antigens have been found to induce partial protection against experimental infection with M. tuberculosis, 5-8 M. leprae 9 or M. avium, 10,11 suggesting that non-replicating subunit vaccines may be effective in humans. However, of the 18 different anti-tuberculosis DNA vaccines reported thus far, none were more effective than BCG (reviewed in 12).…”

Section: Introductionmentioning

confidence: 99%

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The combination of plasmid interleukin‐12 with a single DNA vaccine is more effective than Mycobacterium bovis (bacille Calmette–Guèrin) in protecting against systemic Mycobacterim avium infection

et al. 2003

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SUMMARYSub-unit vaccines utilizing purified mycobacterial proteins or DNA vaccines induce partial protection against mycobacterial infections. For example, immunization with DNA vaccines expressing the gene for the immunodominant 35 000 MW protein, common to Mycobacterium avium and Mycobacterium leprae but absent from the Mycobacterium tuberculosis complex, conferred significant protection against infection with either virulent M. avium or M. leprae in mice. However, the level of protection was equivalent to that obtained with the viable, attenuated vaccine, Mycobacterium bovis, bacille Calmette-Guèrin (BCG). The cytokine, interleukin (IL)-12, is essential for priming naïve CD4 þ T lymphocytes to differentiate into interferon-g (IFN-g)-secreting T cells. We have used a novel self-splicing vector expressing both chains of murine IL-12 to determine if plasmid IL-12 would increase the efficacy of a vaccine expressing the M. avium 35 000 MW protein (DNA-Av35). Co-immunization with p2AIL-12 and DNA-Av35 led to a significant increase in the number of antigen-specific IFN-g secreting cells and total amount of IFNg released, but a concomitant fall in the antibody response to the 35 000 MW protein. This pattern of response was associated with enhanced clearance of M. avium from the liver and spleen of coimmunized mice, and was significantly more effective than BCG or DNA-Av35. alone. Following M. avium challenge there was significant increase in the expansion of the 35 000 MW antigen-reactive T cells in the coimmunized mice. Therefore, plasmid-delivered IL-12 acts as an effective adjuvant to increase the protective efficacy of a single DNA vaccine against M. avium infection above that achieved by BCG, and this strategy may improve the efficacy of subunit vaccines against M. leprae and M. tuberculosis.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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The combination of plasmid interleukin‐12 with a single DNA vaccine is more effective than Mycobacterium bovis (bacille Calmette–Guèrin) in protecting against systemic Mycobacterim avium infection

et al. 2003

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“…New vaccines must be able to make the gastrointestinal tract of domestic livestock a hostile place as well. Investment in research is required in order to produce effective DNA vaccines for MAP (367,368) and disabled mutant strains of MAP using gene knockout (369). Candidate vaccines can then be given to young animals intranasally or by other means that ensure the acquisition of mucosal, as well as systemic, protection.…”

Section: Prospects For Preventive Andmentioning

confidence: 99%

Causation of Crohn’s Disease byMycobacterium aviumSubspeciesParatuberculosis

Hermon‐Taylor

Bull

Sheridan

et al. 2000

Canadian Journal of Gastroenterology

201

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Mycobacterium avium subspecies paratuberculosis (MAP) is a member of the M avium complex (MAC). It differs genetically from other MAC in having 14 to 18 copies of IS900 and a single cassette of DNA involved in the biosynthesis of surface carbohydrate. Unlike other MAC, MAP is a specific cause of chronic inflammation of the intestine in many animal species, including primates. The disease ranges from pluribacillary to paucimicrobial, with chronic granulomatous inflammation like leprosy in humans. MAP infection can persist for years without causing clinical disease. The herd prevalence of MAP infection in Western Europe and North America is reported in the range 21% to 54%. These subclinically infected animals shed MAP in their milk and onto pastures. MAP is more robust than tuberculosis, and the risk that is conveyed to human populations in retail milk and in domestic water supplies is high. MAP is harboured in the ileocolonic mucosa of a proportion of normal people and can be detected in a high proportion of full thickness samples of inflamed Crohn's disease gut by improved culture systems and IS900 polymerase chain reaction if the correct methods are used. MAP in Crohn's disease is present in a protease-resistant nonbacillary form, can evade immune recognition and probably causes an immune dysregulation. As with other MAC, MAP is resistant to most standard antituberculous drugs. Treatment of Crohn's disease with combinations of drugs more active against MAC such as rifabutin and clarithromycin can bring about a profound improvement and, in a few cases, apparent disease eradication. New drugs as well as effective MAP vaccines for animals and humans are needed. The problems caused by MAP constitute a public health issue of tragic proportions for which a range of remedial measures are urgently needed.

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“…BCG reduces the incidence of M. avium infection in humans [4]. However, BCG offers only moderate levels of protection in animal models [5,6]. A more effective vaccine combined with MDT may contribute to the control of M. avium infections.…”

Section: Introductionmentioning

confidence: 99%

Comparative protective effects of recombinant DNA andMycobacterium bovisbacille Calmette–Guérin vaccines againstM. aviuminfection

Martin

Triccas²,

Kamath³

et al. 2001

Clinical and Experimental Immunology

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SUMMARYA range of strategies are being explored to develop more effective vaccines against mycobacterial infection, including immunization with DNA plasmids encoding single mycobacterial bacterial genes and the use of recombinant live vectors based on the current vaccine, Mycobacterium bovis bacille Calmette±Gue Ârin (BCG). We have compared these two approaches using a model of virulent M. avium infection, and the gene for the immunodominant 35 kDa protein which is shared by M. avium and M. leprae, but absent from BCG. Recombinant BCG over-expressing the M. avium 35 kDa protein (BCG-35) induced strong antigen-specific proliferative and interferon-g (IFN-g)-secreting T cell responses. These were comparable to those induced by a single immunization with a plasmid expressing the same antigen (DNA-35); however, repeat DNA-35 immunization evoked the strongest IFN-g release. Immunization with BCG-35 significantly reduced the growth of virulent M. avium, although this effect was similar to that induced by wild-type BCG. Immunization with DNA-35 resulted in significantly greater (2 Â log 10 ) reduction in the growth of M. avium. Prime-boost strategies combining DNA-35 and BCG-35 increased the protective effect above that achieved by BCG-35, but they were not more protective than DNA-35 alone. Therefore, recombinant BCG-35 and BCG induced similar levels of protection in this model, and maximal protection against M. avium infection was attained by immunization with DNA encoding the 35 kDa protein.

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Protection againstMycobacterium aviumby DNA Vaccines Expressing Mycobacterial Antigens as Fusion Proteins with Green Fluorescent Protein

Cited by 38 publications

References 44 publications

The combination of plasmid interleukin‐12 with a single DNA vaccine is more effective than Mycobacterium bovis (bacille Calmette–Guèrin) in protecting against systemic Mycobacterim avium infection

The combination of plasmid interleukin‐12 with a single DNA vaccine is more effective than Mycobacterium bovis (bacille Calmette–Guèrin) in protecting against systemic Mycobacterim avium infection

Causation of Crohn’s Disease byMycobacterium aviumSubspeciesParatuberculosis

Comparative protective effects of recombinant DNA andMycobacterium bovisbacille Calmette–Guérin vaccines againstM. aviuminfection

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