1. Overview of the Laboratory of Respiratory and Special Pathogens Michael Schmitt, Ph.D. Chief, Laboratory of Respiratory and Special Pathogens

2. Overview of LRSP   Principal Investigators in LRSP – Research/Reviewers: -To develop and direct a research program -Participate in the regulatory activities of LRSP.   The research is broad in scope--and varies from basic studies that address questions on bacterial virulence --to studies that provide insight into the functional characteristics of current and future vaccines   The research is supportive of the regulatory activities of the laboratory…Product review for a diverse group of bacterial vaccines

3. Regulatory Responsibilities Primary Licensed Vaccines (combinations) Diphtheria vaccines Tetanus vaccines Pertussis vaccines Bio-defense Vaccines   Anthrax vaccines (licensed) Plague vaccines Botulinum vaccines Ricin Vaccines Other Vaccines Staphylococcus aureus vaccines Streptococcal vaccines Clostridial vaccines

4. Regulatory activities   Pre-approval  Review of IND and IND amendments  Review of BLAs  Post-approval  BLA supplements (product or clinical)  Lot release  Inspections

5. Current Organization of LRSP

6. LRSP Staff

7. Regulatory Activities of LRSP Regulatory

8. Burns Research Program Anthrax vaccines Analysis of the antibody response to anthrax vaccines Improving anthrax vaccine stability Staphylococcus aureus vaccines Identification of potential vaccine antigens Elucidation of correlates of immunity

9. Burns Research Program Facilitates optimization of manufacturing methods for anthrax vaccines Facilitates optimization of manufacturing methods for anthrax vaccines Provides information used in the development of quality control tests for anthrax and S. aureus vaccines Provides information used in the development of quality control tests for anthrax and S. aureus vaccines Supplies important information for assessing efficacy of new anthrax and S. aureus vaccines Supplies important information for assessing efficacy of new anthrax and S. aureus vaccines

10. Keller Research Program Botulinum and Tetanus Toxoid Vaccines Improve toxoid testing strategies resulting in improved antigen quality control Develop assays to better assess the quality of botulinum and tetanus antibodies Evaluate antitoxin preparations for use as reference standards

11. Keller Research Program Fosters development of improved botulinum toxoid vaccines and antitoxins to enhance preparedness against bioterror attacks Fosters development of improved botulinum toxoid vaccines and antitoxins to enhance preparedness against bioterror attacks Provides the scientific foundation for evaluating botulinum toxoid and tetanus toxoid vaccines Provides the scientific foundation for evaluating botulinum toxoid and tetanus toxoid vaccines

12. Merkel Research Program Pertussis vaccines Development and use of the baboon model of pertussis to study pertussis pathogenesis and the immune response to infection and vaccination. Development of aerosol models of pertussis to identification and characterize factors contributing to transmission of B. pertussis Anthrax vaccines Development of cost-effective models of pulmonary anthrax for screening and early development of anthrax vaccines and therapeutic products Characterization of innate immune recognition of pulmonary anthrax Staphylococcus aureus vaccines Development of models of staphylococcal systemic, implant, and skin infections for evaluating candidate vaccine antigens

13. Merkel Research Program Provides important insights into vaccine-mediated protection against pertussis leading to enhanced understanding of the resurgence of pertussis in the U.S. and potential public health responses to the pertussis problem. Provides important insights into vaccine-mediated protection against pertussis leading to enhanced understanding of the resurgence of pertussis in the U.S. and potential public health responses to the pertussis problem. Furthers development of new vaccines and post-exposure treatments for pertussis, anthrax and S. aureus infections Furthers development of new vaccines and post-exposure treatments for pertussis, anthrax and S. aureus infections Provides resources critical for the early development and evaluation of new bacterial vaccines Provides resources critical for the early development and evaluation of new bacterial vaccines Provides the scientific foundation for evaluation of pertussis, anthrax, and S. aureus vaccines Provides the scientific foundation for evaluation of pertussis, anthrax, and S. aureus vaccines

14. Schmitt Research Program Diphtheria Vaccines Characterization of the Hmu iron transport system of Corynebacterium diphtheriae Proteins of this system are coordinately expressed with diphtheria toxin and are therefore expected to be produced during infection Cell surface components of this system share similarity with virulence in other disease-causing gram positive bacteria Analysis of heme-dependent regulatory systems of C. diphtheriae

15. Schmitt Research Program Provides a better understanding of pathogenic mechanisms of C. diphtheriae facilitating development of new or improved diphtheria vaccines Provides a better understanding of pathogenic mechanisms of C. diphtheriae facilitating development of new or improved diphtheria vaccines Provides information about potential new immunogens for gram-positive bacterial vaccines Provides information about potential new immunogens for gram-positive bacterial vaccines Provides the scientific foundation for evaluation of new vaccines containing diphtheria components as well as review of the numerous ongoing changes and adjustments required to maintain and improve the quality of licensed diphtheria toxoid-containing vaccines Provides the scientific foundation for evaluation of new vaccines containing diphtheria components as well as review of the numerous ongoing changes and adjustments required to maintain and improve the quality of licensed diphtheria toxoid-containing vaccines Of note, approximately 25% of all licensed vaccines distributed in the U.S contain a diphtheria toxoid component.

16. Relevance of Research to Regulation Knowledge acquired from our research establishes a scientific basis for our decisions in the regulations of vaccines. Knowledge acquired from our research establishes a scientific basis for our decisions in the regulations of vaccines.  Provides a in-depth understanding of novel products  Expertise to best design the tests to assess the safety, purity and potency of vaccines  Expertise to design the efficacy studies for vaccines licensed under the Animal Rule  Credibility in the scientific community. Provides assurances that we possess the scientific qualifications to assess safety and quality of current and the next generation of vaccines