Bovine tuberculosis (TB) continues to be a major health problem in cattle and development of a safe effective vaccine to control TB in cattle would be very useful. This paper reviews progress and provides new data in development of a TB bio-bead vaccine based on polyester nanoparticle inclusions which were produced by bioengineered bacteria. Polyhydroxybutyrate (PHB) biopolyester nanoparticles (bio-beads) have been produced which displayed mycobacterial antigens, Ag85A and ESAT-6, on the surface of the bio-beads for use as vaccines for the control of tuberculosis. Bio-beads were purified from the host production bacteria, Escherichia coli and the generally regarded as safe (GRAS) bacterium, Lactococcus lactis. Previous published studies showed that vaccination with Ag85A/ESAT-6 bio-beads induced antigen-specific IFN-γ, IL-17A, IL-6, TNF-α and IL-2 in splenocytes, but no significant increase in IL-4, IL-5 or IL-10. New results showed that antigen-specific IFN-γ release was induced by both CD4 and CD8 T cells in mice vaccinated with the Ag85A/ESAT-6 bio-beads. Mice vaccinated with Ag85A/ESAT-6 bio-beads alone or in combination with BCG had significantly lower bacterial counts from the lungs and spleen following aerosol challenge with Mycobacterium bovis compared to control groups. This unique approach to the design and production of bacterial-derived bio-beads displaying antigens enables a cost-effective way to express a diverse antigen repertoire for use as vaccines to combat TB or other diseases.

2013-11-01·Journal of Applied Microbiology3区 · 生物学

CpG7909 adjuvant enhanced immunogenicity efficacy in mice immunized with ESAT6-Ag85A fusion protein, but does not confer significant protection against Mycobacterium tuberculosis infection

3区 · 生物学

Article

作者: Deng, H. ; Chen, H. ; Hu, S. ; Shi, C. ; Ma, J. ; Huang, H. ; Gong, F. ; Chen, Q.

AIMSThis study aimed to investigate the ability of CpG7909 adjuvant to enhance immunogenicity and protective efficacy of a subunit vaccine composed of ESAT6-Ag85A fusion protein (Pe685a) of Mycobacterium tuberculosis.METHODS AND RESULTSELISA was used to detect specific antibody and IFN-γ expression in sera; ELISPOT, to detect IFN-γ expression in splenocytes; MTT assay and FACS, to detect T-lymphocytes proliferation in spleens; and RT-PCR, to detect cytokines expression in lungs of mice after immunization. Bacterial load and histopathological lesions in lungs or spleens of mice challenged with Myco. tuberculosis H37Rv strain were analysed. Compared with incomplete Freund's adjuvant, CpG7909 induced more potent production of Pe685a-specific IgG2a/IgG1 antibody and higher expression of IFN-γ in sera, stimulated more generation of antigen-specific IFN-γ-secreting splenocytes, enhanced frequencies of CD3(+) CD4(+) and CD3(+) CD8(+) T-lymphocytes in spleen and increased transcription of TNF-α, IFN-γ, IL-6 and TLR9 in lung. However, lower bacterial load in lung and less severe lung pathology were not observed in CpG7909 group mice.CONCLUSIONSCpG7909 is able to enhance immunological effects of Pe685a subunit vaccine, but does not confer significant protective efficacy against Myco. tuberculosis infection.SIGNIFICANCE AND IMPACT OF THE STUDYCpG7909 as an adjuvant of subunit vaccine against Myco. tuberculosis is worthy of further investigation.

2012-01-01·Clinical and Vaccine Immunology

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

Article

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

ABSTRACT New improved vaccines are needed for control of both bovine and human tuberculosis. Tuberculosis protein vaccines have advantages with regard to safety and ease of manufacture, but efficacy against tuberculosis has been difficult to achieve. Protective cellular immune responses can be preferentially induced when antigens are displayed on small particles. In this study, Escherichia coli and Lactococcus lactis were engineered to produce spherical polyhydroxybutyrate (PHB) inclusions which displayed a fusion protein of Mycobacterium tuberculosis , antigen 85A (Ag85A)–early secreted antigenic target 6-kDa protein (ESAT-6). L. lactis was chosen as a possible production host due its extensive use in the food industry and reduced risk of lipopolysaccharide contamination. Mice were vaccinated with PHB bead vaccines with or without displaying Ag85A–ESAT-6, recombinant Ag85A–ESAT-6, or M. bovis BCG. Separate groups of mice were used to measure immune responses and assess protection against an aerosol M. bovis challenge. Increased amounts of antigen-specific gamma interferon, interleukin-17A (IL-17A), IL-6, and tumor necrosis factor alpha were produced from splenocytes postvaccination, but no or minimal IL-4, IL-5, or IL-10 was produced, indicating Th1- and Th17-biased T cell responses. Decreased lung bacterial counts and less extensive foci of inflammation were observed in lungs of mice receiving BCG or PHB bead vaccines displaying Ag85A–ESAT-6 produced in either E. coli or L. lactis compared to those observed in the lungs of phosphate-buffered saline-treated control mice. No differences between those receiving wild-type PHB beads and those receiving recombinant Ag85A–ESAT-6 were observed. This versatile particulate vaccine delivery system incorporates a relatively simple production process using safe bacteria, and the results show that it is an effective delivery system for a tuberculosis protein vaccine.

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