Vaccines Displaying Mycobacterial Proteins on Biopolyester Beads Stimulate Cellular Immunity and Induce Protection against Tuberculosis

Parlane, Natalie A.; Grage, Katrin; Mifune, Jun; Basaraba, Randall J.; Wedlock, D. Neil; Rehm, Bernd H. A.; Buddle, Bryce M.

doi:10.1128/cvi.05505-11

Cited by 63 publications

(72 citation statements)

References 54 publications

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“…5). Parlane et al also demonstrated the induction of a protective response in mice vaccinated with similar polyester particles expressing antigens Ag85A-ESAT6 which was superior to that induced by soluble antigens (62). The versatility and potential of the bead antigen delivery system in eliciting different complementary facets of the immune response could be applied to the development of multivalent vaccines (52).…”

Section: Discussionmentioning

confidence: 99%

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System

Martínez‐Donato

Piniella

Aguilar

et al. 2016

Clin Vaccine Immunol

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Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain ( Hepatitis C virus (HCV) is an etiologic agent of chronic hepatitis C (1). Chronic HCV infection affects more than 170 million people worldwide and is responsible for approximately 350,000 deaths each year (2). Viral exposure results in acute disease in a small proportion of cases, while the majority (80%) progress to chronic infection, causing liver inflammation that slowly progresses to cirrhosis, liver failure, hepatocellular carcinoma, and death (3).Despite a substantial decline in HCV transmission due to improved prevention strategies and the introduction of new and powerful targeted therapies, hepatitis C remains a huge health problem, justifying further endeavors to develop new vaccines. Indeed, the pool of asymptomatic chronic HCV carriers who represent an infectious reservoir will remain substantial for many years. Less than 30% of patients with chronic hepatitis C are aware of the infection, and only about 10% of patients are currently treated (4, 5). Therefore, even if new antivirals could cure 90% of patients, there would still be a considerable percentage of patients who would be excluded (6). Hence, development of a vaccine to prevent infection or to at least prevent progression to chronicity represents a significant unmet medical need and is of high priority.Since 1% of infected patients show an immune response clearing the infection and the rate of spontaneous resolution is higher in the case of reinfected patients, this demonstrates that the induction of protective immunity which prevents development of chronic disease is a feasible goal for the development of a preventive vaccine against HCV (7,8).The role of HCV-specific T cell responses in the outcome of primary HCV infection has been widely studied, although a single correlate of protection has not been determined. However, it is known that this type of immune response is a determinant in the clearance of the virus. Comparative studies in humans and chimpanzees have shown that widespread and long-lasting CD8 ϩ and CD4 ϩ T cell responses against multiple HCV regions are linked to spontaneous viral clearance (9, 10).However, there is also strong evidence that rapid induction of high-titer cross-neutralizing antibodies targeting HCV envelope proteins correlates with viral clearance and protects against reinfection (11, 12). Therefore, an optimal HCV vaccine probably needs to elicit broad cross-reactive cellular immune responses together with cross-neutralizing antibo...

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Section: Discussionmentioning

confidence: 99%

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System

Martínez‐Donato

Piniella

Aguilar

et al. 2016

Clin Vaccine Immunol

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“…The addition of Rv3615c to the reagent containing ESAT6 and CFP10 significantly improves the sensitivity of skin tests in the naturally infected cattle and does not cause responses in vaccinated or healthy cattle (3), indicating that the use of a protein cocktail of CFP10, ESAT6, and Rv3615c would be beneficial for TB skin testing. Furthermore, antigens from pathogenic mycobacteria, such as antigen 85A and ESAT6, had been shown to stimulate stronger cellular immune responses when they were displayed on the surface of polyester beads than when they were free antigens (24). Accordingly, CFP10-Rv3615c-ESAT6 immobilized on the surface of a polyester bead might act as a more sensitive and cost-effectively producible diagnostic reagent than the respective free antigens.…”

Section: Discussionmentioning

confidence: 99%

“…These polyester beads showed immunogenicity in vivo leading to specific Th1 and Th2 immune responses (14,23,24). The aim of this study was to genetically engineer E. coli to produce fusion proteins which mediate formation of polyester beads displaying selected TB antigens (CFP10, ESAT6, and Rv3615c) suitable for TB skin test applications.…”

Section: Discussionmentioning

confidence: 99%

“…Foreign target proteins have been displayed on polyester beads for subsequent cleavage and purification (19)(20)(21)(22). Polyester beads displaying antigens were found to be immunogenic and mediated Th1 and Th2 immune responses leading to protective immunity against TB (14,23,24). Hence, custom-made polyester beads displaying selected TB antigens might serve as a specific TB diagnostic reagent in skin tests.…”

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confidence: 99%

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New Skin Test for Detection of Bovine Tuberculosis on the Basis of Antigen-Displaying Polyester Inclusions Produced by Recombinant Escherichia coli

Chen

Parlane

Lee

et al. 2014

Appl Environ Microbiol

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cThe tuberculin skin test for diagnosing tuberculosis (TB) in cattle lacks specificity if animals are sensitized to environmental mycobacteria, as some antigens in purified protein derivative (PPD) prepared from Mycobacterium bovis are present in nonpathogenic mycobacteria. Three immunodominant TB antigens, ESAT6, CFP10, and Rv3615c, are present in members of the pathogenic Mycobacterium tuberculosis complex but absent from the majority of environmental mycobacteria. These TB antigens have the potential to enhance skin test specificity. To increase their immunogenicity, these antigens were displayed on polyester beads by translationally fusing them to a polyhydroxyalkanoate (PHA) synthase which mediated formation of antigen-displaying inclusions in recombinant Escherichia coli. The most common form of these inclusions is poly(3-hydroxybutyric acid) (PHB). The respective fusion proteins displayed on these PHB inclusions (beads) were identified using tryptic peptide fingerprinting analysis in combination with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The surface exposure and accessibility of antigens were assessed by enzyme-linked immunosorbent assay (ELISA). Polyester beads displaying all three TB antigens showed greater reactivity with TB antigen-specific antibody than did beads displaying only one TB antigen. This was neither due to cross-reactivity of antibodies with the other two antigens nor due to differences in protein expression levels between beads displaying single or three TB antigens. The triple-antigen-displaying polyester beads were used for skin testing of cattle and detected all cattle experimentally infected with M. bovis with no false-positive reactions observed in those sensitized to environmental mycobacteria. The results suggested applicability of TB antigen-displaying polyester inclusions as diagnostic reagents for distinguishing TB-infected from noninfected animals.

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“…Foreign proteins have been displayed on the polyester beads by translationally fusing them to a polyester synthase (PhaC), which has mediated formation of protein-displaying beads in recombinant E. coli (15,16). The beads are 100 to 500 nm in diameter, and beads contain an amorphous hydrophobic polyester core surrounded by proteins, including the fusion protein composed of PhaC and foreign proteins (12,17). Interestingly, immunological studies using antigen-displaying beads revealed that the beads showed adjuvant properties by enhancing the immune response to the displayed antigen, compared to its soluble counterpart (18).…”

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confidence: 99%

Display of Antigens on Polyester Inclusions Lowers the Antigen Concentration Required for a Bovine Tuberculosis Skin Test

Parlane

Chen

Jones

et al. 2016

Clin Vaccine Immunol

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eThe tuberculin skin test is the primary screening test for the diagnosis of bovine tuberculosis (TB), and use of this test has been very valuable in the control of this disease in many countries. However, the test lacks specificity when cattle have been exposed to environmental mycobacteria or vaccinated with Mycobacterium bovis bacille Calmette-Guérin (BCG). Recent studies showed that the use of three or four recombinant mycobacterial proteins, including 6-kDa early secretory antigenic target (ESAT6), 10-kDa culture filtrate protein (CFP10), Rv3615c, and Rv3020c, or a peptide cocktail derived from those proteins, in the skin test greatly enhanced test specificity, with minimal loss of test sensitivity. The proteins are present in members of the pathogenic Mycobacterium tuberculosis complex but are absent in or not expressed by the majority of environmental mycobacteria and the BCG vaccine strain. To produce a low-cost skin test reagent, the proteins were displayed at high density on polyester beads through translational fusion to a polyhydroxyalkanoate synthase that mediates the formation of antigen-displaying inclusions in recombinant Escherichia coli. Display of the proteins on the polyester beads greatly increased their immunogenicity, allowing for the use of very low concentrations of proteins (0.1 to 3 g of mycobacterial protein/inoculum) in the skin test. Polyester beads simultaneously displaying all four proteins were produced in a single fermentation process. The polyester beads displaying three or four mycobacterial proteins were shown to have high sensitivity for detection of M. bovis-infected cattle and induced minimal responses in animals exposed to environmental mycobacteria or vaccinated with BCG. C ontrol of bovine tuberculosis (TB), which is caused by infection with Mycobacterium bovis, is critical, as this disease is of great economic and zoonotic importance. Programs for eradication in cattle are primarily based on use of the tuberculin skin test for diagnosis of the disease, with slaughter of reactor animals. This approach has been instrumental in eradication of this disease from a number of countries (1). The tuberculin skin test is a delayedtype hypersensitivity (DTH) test that was developed more than 100 years ago for the diagnosis of TB, and it has proved to be a simple, inexpensive, robust, and widely accepted test. However, the test lacks specificity when animals have been sensitized to environmental mycobacteria or have been vaccinated with the human TB vaccine, M. bovis bacille Calmette-Guérin (BCG) (2). Estimates of sensitivity for a single intradermal test in cattle using purified protein derivative (PPD) prepared from M. bovis (bovine PPD) have ranged from 63.2% to 100% (median, 83.9%), with specificity between 75.5% and 99.0% (median, 96.8%) (reviewed in reference 2). Development of a more specific skin test reagent would be highly desirable. The use of BCG vaccine alone or as part of a heterologous prime-boost combination is currently being considered by a number of countries fo...

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Vaccines Displaying Mycobacterial Proteins on Biopolyester Beads Stimulate Cellular Immunity and Induce Protection against Tuberculosis

Cited by 63 publications

References 54 publications

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System

New Skin Test for Detection of Bovine Tuberculosis on the Basis of Antigen-Displaying Polyester Inclusions Produced by Recombinant Escherichia coli

Display of Antigens on Polyester Inclusions Lowers the Antigen Concentration Required for a Bovine Tuberculosis Skin Test

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