Novel tuberculosis vaccines on the horizon.

Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
Current opinion in immunology (Impact Factor: 7.87). 06/2010; 22(3):374-84. DOI: 10.1016/j.coi.2010.04.006
Source: PubMed

ABSTRACT Eleven new tuberculosis (TB) vaccines are in various phases of clinical trials. These include subunit vaccines to improve the current vaccine BCG, and recombinant BCG to substitute for BCG, both given pre-exposure to prevent active disease. A plethora of potential candidates have reached various stages of the pre-clinical development pipeline, some ready to enter Phase I clinical trial soon. A boost vaccine to top up the immunity of existing BCG is on the horizon and will have to suffice until a better candidate to replace BCG is ready. The live mutants of Mycobacterium tuberculosis show great promise, but face a myriad of regulatory challenges.

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    • "One of the focuses of vaccine development is to combine multiple epitopes in the same construct, with the aim of achieving a broader and more potent response than whole-protein vaccines (Parida and Kaufmann, 2010). To streamline the selection of epitopes for this purpose, microarray and immuno-informatics have been used. "
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    ABSTRACT: Since its publication in 1998, the genome sequence of the Mycobacterium tuberculosis H37Rv laboratory strain has acted as the cornerstone for the study of tuberculosis. In this review we address some of the practical aspects that have come to light relating to the use of H37Rv throughout the past decade which are of relevance for the ongoing genomic and laboratory studies of this pathogen. These include errors in the genome reference sequence and its annotation, as well as the recently detected variation amongst isolates of H37Rv from different laboratories.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 06/2011; 12(4):807-10. DOI:10.1016/j.meegid.2011.06.011 · 3.26 Impact Factor
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    • "Perhaps the unstable structure feature is one of possible reasons for ESAT-6 low inherent immunogenicity that is not sufficient to elicit specific protective immunity against M. tb infection by itself. Many studies have tried to fuse ESAT-6 with other TB antigens or carrier proteins to enhance its immunogenicity [4] [5] [6] [7] [8] [9] [10] [11]. For the instance, in the new promising TB vaccine H56, ESAT-6 was fused with two other TB antigens Ag85B and Rv2660c [7]. "
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    ABSTRACT: Early secreted antigenic target-6 (ESAT-6), an important Mycobacterium tuberculosis T-cell antigen, is an attractive candidate antigen for tuberculosis subunit vaccine development. Because ESAT-6 has a low inherent immunogenicity, we used Hepatitis B virus core (HBc) protein as an immune carrier to enhance ESAT-6 immunogenicity. The ESAT-6 gene was inserted into the major immunodominant region of the HBc molecule by fusion PCR. The recombinant protein, HBc-ESAT-6 (HE6), was expressed in Escherichia coli, and electron microscopy confirmed the formation of virus-like particles. The immunogenicity of the chimeric particles was assessed in mice. Serological assays and in vitro Th1-biased cytokine assays found that immunization with HE6 particles elicited significantly higher ESAT-6-specific antibodies and CD4⁺/CD8⁺ T cell responses in mice compared to immunization with recombinant ESAT-6 protein. These data demonstrate the feasibility of HBc particles serving as an efficient immune carrier for ESAT-6 and suggest that HE6 has potential for use in a tuberculosis subunit vaccine.
    Vaccine 06/2011; 29(34):5645-51. DOI:10.1016/j.vaccine.2011.06.012 · 3.49 Impact Factor
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    • "While new vaccines are currently in development [5] [6], BCG remains the only TB vaccine approved for human use. Thus, one promising avenue is to develop adjuvants that are capable of improving efficacy of the existing BCG vaccine. "
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    ABSTRACT: The goal of vaccination to prevent tuberculosis disease (TB) is to offer long-term protection to the individual and the community. In addition, the success of any protective TB vaccine should include the ability to limit cavitary formation and disease progression. The current BCG vaccine protects against disseminated TB disease in children by promoting development of antigenic-specific responses. However, its efficacy is limited in preventing postprimary pulmonary disease in adults that is responsible for the majority of disease and transmission. This paper illustrates the use of lactoferrin as an adjuvant to boost efficacy of the BCG vaccine to control organism growth and limit severe manifestation of pulmonary disease. This resulting limitation in pathology may ultimately, limit spread of bacilli and subsequent transmission of organisms between individuals. The current literature is reviewed, and data is presented to support molecular mechanisms underlying lactoferrin's utility as an adjuvant for the BCG vaccine.
    04/2011; 2011:835410. DOI:10.1155/2011/835410
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