Construction of an encapsulated ESAT-6-based anti-TB DNA vaccine and evaluation of its immunogenic properties

Nosareva, Olesya V.; Nesterov, Andrey E.; Boldyrev, Alexander A.; Смирнова, О. В.; Tumanov, Yurii; Kouzmitcheva, G.; Tat'kov, S. I.

doi:10.1515/bc.2008.063

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…Since IFN-g plays an important role in the induction of protective responses, its production is often used as a key indicator for evaluating the effectiveness of vaccines. IFN-g is produced by Th1-like cells, released early upon encapsulated CFP-10:ESAT-6-based anti-TB DNA vaccine T-cell activation, and in our experiment, increased levels of IFN-g were associated with stimulating splenocyte proliferation [27]. The increase in the IFN-g levels demonstrated a change toward the cellular immune response (Th1) in mice [28].…”

Section: Discussionsupporting

confidence: 53%

<italic>Marek's disease virus</italic> VP22 enhances potentially the immune response of ESAT-6/CFP-10 against <italic>Mycobacterium bovis</italic> infection

Chen¹,

Wang²,

Chen³

et al. 2010

ABBS

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Currently available vaccines against Mycobacterium bovis, the causative agent of tuberculosis, do not provide reliable efficacy and there is therefore a need for a novel vaccine with improved efficacy. Here, we use protein transduction technology to deliver DNA vaccines expressing mycobacterial antigens directly to target cells. We used various protein transduction domain (PTD) proteins including the VP22 conjugate from Marek's disease virus serotype 1 (MDV-1), as delivery systems for DNA constructs encoding the antigens early secretory antigenic target-6 kDa (ESAT-6) protein and culture filtrate protein 10 (CFP-10) of M. bovis. The eukaryotic expression plasmid pZ106, encoding antigens ESAT-6 and CFP-10, conjugated to various PTDs, was used to construct experimental preparations. Our findings demonstrated that VP22 alone or in combination with CFP-10:ESAT-6 fusion protein could spread into all the nuclei of the cell monolayer surrounding the transfected cells. Whereas trans-activating transcriptional PTD showed limited delivery of the fusion protein and 8R peptide was unable to deliver the fusion protein into any untransfected cells. We have demonstrated that immunization with a preparation fused to VP22 leads to a higher antibody and interferon-g titer (P < 0.05). Taken together, our results demonstrated that MDV-1 VP22 serves as a potential immune enhancer in gene therapy and immunization using DNA vaccines, offering a novel approach for the prevention of M. bovis infection.

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Section: Discussionsupporting

confidence: 53%

<italic>Marek's disease virus</italic> VP22 enhances potentially the immune response of ESAT-6/CFP-10 against <italic>Mycobacterium bovis</italic> infection

Chen¹,

Wang²,

Chen³

et al. 2010

ABBS

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“…Our rM.S-e6c10 vaccine expressed the ESAT6-CFP10 fusion protein in M. smegmatis as shown by Western blot. Interestingly, it induced higher levels of IFN-c and IL-2 than did ESAT6 or ESAT6-Flt (Flt3 ligand) [31,32]. This suggests a more intense cellular immunity response is induced by the fusion protein.…”

Section: Discussionmentioning

confidence: 95%

Recombinant Mycobacterium smegmatis Expressing an ESAT6‐CFP10 Fusion Protein Induces Anti‐Mycobacterial Immune Responses and Protects Against Mycobacterium tuberculosis Challenge in Mice

et al. 2010

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The currently used vaccine against tuberculosis, Bacille Calmette‐Guérin (BCG), has variable efficacy, so new vaccine development is crucial. In this study, we evaluated a recombinant vaccine prepared from non‐pathogenic Mycobacterium smegmatis (rMS) that expresses a fusion of early secreted antigenic target 6‐kDa antigen (ESAT6) and culture filtrate protein 10 (CFP10). C57BL/6 mice were immunized with the rMS expressing the ESAT6‐CFP10 fusion protein (rM.S‐e6c10) or with BCG. The mice in the rM.S‐e6c10 group had a significantly higher titre of anti‐ESAT6‐CFP10 antibodies than did animals in the BCG or saline groups. Spleen cells from rM.S‐e6c10‐immunized mice exhibited a cytotoxic response to ESAT6 and CFP10‐expressed target cells, but spleen cells from animals in the other groups did not. Levels of IFN‐γ and IL‐2 production by purified T cells from spleens were significantly higher in rM.S‐e6c10 group than in BCG group. Finally, after M. tuberculosis (MTB)‐challenged mice, dramatic reduction in the numbers of MTB colony‐forming units (CFUs) in the lungs was observed for the mice immunized with the rMS. The protective efficacy of rM.S‐e6c10 and BCG vaccination was similar based on measures of MTB burden and lung pathology. Our data indicate that the recombinant M. smegmatis vaccine expressing the ESAT6‐CFP10 fusion protein has potential in clinic application.

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“…Recombinant BCG expressing ESAT-6 also conferred enhanced immunogenicity and protection against TB when compared with the parent BCG vaccine [29, 30]. Other vaccine platforms such as DNA vaccine [31–33], Influenza virus [34], and Salmonella typhimurium [35] also demonstrated that ESAT-6 is a potential immunodominant antigen for the development of TB vaccines. In addition, a chimeric protein of Ag85A and ESAT-6 with strong immunogenicity showed a treatment effect on MDR-TB in mice [36, 37].…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Protective Efficacy against Murine Tuberculosis of a Prime-Boost Regimen with BCG and a DNA Vaccine Expressing ESAT-6 and Ag85A Fusion Protein

Wang

Zhou

et al. 2011

Clinical and Developmental Immunology

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Heterologous prime-boost regimens utilizing BCG as a prime vaccine probably represent the best hope for the development of novel tuberculosis (TB) vaccines. In this study, we examined the immunogenicity and protective efficacy of DNA vaccine (pcD685A) expressing the fusion protein of Ag85A and ESAT-6 (r685A) and its booster effects in BCG-immunized mice. The recombinant r685A fusion protein stimulated higher level of antigen-specific IFN-γ release in tuberculin skin test- (TST-) positive healthy household contacts of active pulmonary TB patients than that in TST-negative population. Vaccination of C57BL/6 mice with pcD685A resulted in significant protection against challenge with virulent Mycobacterium tuberculosis H37Rv when compared with the control group. Most importantly, pcD685A could act as a BCG booster and amplify Th1-type cell-mediated immunity in the lung of BCG-vaccinated mice as shown the increased expression of IFN-γ. The most significant reduction in bacterial load of both spleen and lung was obtained in mice vaccinated with BCG prime and pcD685A DNA booster when compared with BCG or pcD685A alone. Thus, our study indicates that pcD685A may be an efficient booster vaccine against TB with a strong ability to enhance prior BCG immunity.

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Construction of an encapsulated ESAT-6-based anti-TB DNA vaccine and evaluation of its immunogenic properties

Cited by 5 publications

References 14 publications

<italic>Marek's disease virus</italic> VP22 enhances potentially the immune response of ESAT-6/CFP-10 against <italic>Mycobacterium bovis</italic> infection

<italic>Marek's disease virus</italic> VP22 enhances potentially the immune response of ESAT-6/CFP-10 against <italic>Mycobacterium bovis</italic> infection

Recombinant Mycobacterium smegmatis Expressing an ESAT6‐CFP10 Fusion Protein Induces Anti‐Mycobacterial Immune Responses and Protects Against Mycobacterium tuberculosis Challenge in Mice

Immunogenicity and Protective Efficacy against Murine Tuberculosis of a Prime-Boost Regimen with BCG and a DNA Vaccine Expressing ESAT-6 and Ag85A Fusion Protein

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Construction of an encapsulated ESAT-6-based anti-TB DNA vaccine and evaluation of its immunogenic properties

Cited by 5 publications

References 14 publications

&lt;italic&gt;Marek's disease virus&lt;/italic&gt; VP22 enhances potentially the immune response of ESAT-6/CFP-10 against &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt; infection

&lt;italic&gt;Marek's disease virus&lt;/italic&gt; VP22 enhances potentially the immune response of ESAT-6/CFP-10 against &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt; infection

Recombinant Mycobacterium smegmatis Expressing an ESAT6‐CFP10 Fusion Protein Induces Anti‐Mycobacterial Immune Responses and Protects Against Mycobacterium tuberculosis Challenge in Mice

Immunogenicity and Protective Efficacy against Murine Tuberculosis of a Prime-Boost Regimen with BCG and a DNA Vaccine Expressing ESAT-6 and Ag85A Fusion Protein

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<italic>Marek's disease virus</italic> VP22 enhances potentially the immune response of ESAT-6/CFP-10 against <italic>Mycobacterium bovis</italic> infection

<italic>Marek's disease virus</italic> VP22 enhances potentially the immune response of ESAT-6/CFP-10 against <italic>Mycobacterium bovis</italic> infection