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ppt ppt Presentation Transcript

  • Laboratory of Mycobacterial Diseases and Cellular Immunology
    • Center for Biologics Evaluation and Research
  • Laboratory of Mycobacterial Diseases and Cellular Immunology
    • Regulatory Responsibilities
    • Research Accomplishments
    • Activities within the Public Health Community
  • LMDCI – Regulatory Responsibilities
    • Provide pre-clinical guidance
    • Review IND submissions
    • Review BLAs
    • Inspect manufacturing facilities
    • Review product labeling and advertising
    • Review product lot release documents
    • Assist in developing regulatory policy
  • LMDCI – Regulated Products
    • VACCINES
    • TB, malaria, tularemia, Lyme disease,
    • Q fever, leishmania
    • IMMUNOTHERAPEUTICS
    • BCG, M. vaccae
    • DIAGNOSTICS
      • Skin test reagents, devices
  • Regulatory Accomplishments (2003 – 2007)
    • Reviewed >700 IND submissions
    • Participated in 12 pre-IND meetings
    • Approved >30 BLA supplements
    • Reviewed 20 Annual Reports
    • Co-authored 3 FDA Guidance documents
    • Made 18 presentations relevant to the regulatory process
    • Co-organized a NIH/FDA workshop on TB vaccines
  • LMDCI Research
    • Molecular basis of TB and Francisella pathogenesis
    • Immune mechanisms associated with intracellular infections
    • The effectiveness of novel TB vaccines
    • Development of assays to characterize vaccine-related products
  • Research Sections of the Laboratory of Mycobacterial Diseases and Cellular Immunology
    • Molecular Vaccines
    • Mycopathogenesis
    • Immune Mechanisms
  • LMDCI – Molecular Vaccines Section
    • Current staff
    • Sheldon Morris, P.I.
    • Steven Derrick
    • Amy Li Yang
    • JaeHyun Lim
    • Kris Kolibab
    • Collaborators
    • AECOM
    • NIH/VRC
    • NIH/NCI
    • Aeras
    • PHRI
  • LMDCI Research – Molecular Vaccines Section
    • Characterization of live, attenuated
    • M. tuberculosis strains
    • Evaluation of novel TB DNA vaccines
    • Development of assays to facilitate TB vaccine development
  • Molecular Vaccines – Significant Findings
    • Demonstrated the effectiveness of the pro-apoptotic strategy for generating new attenuated M. tuberculosis vaccines
    • Showed that BCG immunization protects against challenge by 10 different M. tuberculosis genotypes
  • Molecular Vaccines – Significant Findings (cont.)
    • Developed pre-clinical assays for assessing the safety and potency of post-exposure and prophylactic TB vaccines
    • Showed that the frequency of multifunctional T cells (expressing IFN-  , TNF-  , and IL2) correlate with the level of vaccine-induced protection against TB
  • LMDCI – Mycopathogenesis Section
    • Current Staff
    • Michael Brennan, P.I.
    • Marcela Parra
    • Nathalie Cadieux
    • Prachi Singh
    • Collaborators
    • Institut Pasteur
    • Univ. of MD
    • Colorado State
    • Univ. of Texas
    • Catholic University
  • LMDCI Research – Mycopathogenesis Section
    • Characterization of the Heparin-Binding Hemagglutinin cell surface protein of Mycobacterium tuberculosis
    • Characterization of the novel PE/PE_PGRS multigene family of Mycobacterium tuberculosis
  • Mycopathogenesis Section – Significant Findings
    • Differences in expression of certain PE_PGRS genes during infection indicate that they provide a novel mechanism of antigenic variation used by M. tuberculosis to evade the host immune response .
    • PE-PGRS proteins interact with mitochondria which may lead to host cell injury and death and provides M. tuberculosis with a mechanism for escaping macrophages and other infected host cells.
  • Mycopathogenesis Section – Significant Findings (cont.)
    • A PE antigen has been identified that elicits a strong TH1-like response and protects against M. tuberculosis challenge in an aerosol TB mouse model. This PE antigen (MaPE) is being pursued as a new TB vaccine candidate.
  • LMDCI – Immune Mechanisms Section
    • Current staff
    • Karen Elkins, P.I.
    • Siobhan Cowley
    • Anda Meierovics
    • Roberto De Pascalis
    • Alicia Chou
    • Samantha Roberts
    • Collaborators
    • NIH/NIAID
    • UNC – Chapel Hill
    • UMD – Baltimore
    • Univ. of Victoria
    • UTSA
    • Univ. of New Mexico
  • LMDCI Research – Immune Mechanisms Section
    • Provide reagents and information for tularemia vaccine research
    • Understand innate immune responses to intracellular bacteria, including F. tularensis and M. tuberculosis
    • Define mechanisms by which B and T cells provide protection against intracellular bacteria, including F. tularensis and M. tuberculosis
  • Immune Mechanisms Section – Significant Findings
    • Membrane TNF-  is a major mediator of the T-cell mediated control of Francisella or M. tuberculosis intramacrophage growth, but IFN-  has only a modest role and is unlikely to be a reliable correlate.
    • Non-CD4/CD8 “double-negative” T cells contribute substantially to adaptive immunity against Francisella and Mycobacteria in mice
    • Francisella spp. contains a major pathogenicity island expressing ~25 virulence-related genes; important to the evaluation of LVS safety
  • Summary of LMDCI Research Accomplishments (2003- 2007)
    • Publications – 45
    • (Nature Med., PNAS, J. Exp. Med., J. Clin. Invest.)
    • Invited Presentations – 55
    • External Funding - 15
  • Involvement with the Public Health Community
    • WHO GAVI committee
    • WHO TB Vaccine Initiative Advisory Board
    • WHO STOP/TB Working Group
    • WHO Tularemia network
    • Standard reagents for the WHO
    • CDC skin test studies
    • BTEP program [ US – Russia ]
  • Involvement with the Public Health Community
    • NIH Study Sections
    • NIH TB Vaccine Review Committee
    • NIH Blue Ribbon Panels
    • Advisory Committee for the Elimination of Tuberculosis
    • Federal TB Task Force
    • Editorial Boards for scientific journals
    • Organization of major scientific meetings
  • LMDCI Outreach Activities
    • Provide reagents and develop assays for tularemia and TB research
    • Characterization and distribution of a Mtb challenge strain and standard BCG vaccine for pre-clinical vaccine testing
    • Development of standard tuberculins
    • Distribution of anti-HBHA Mabs and HBHA knock-out strains