1. Division of Bacterial, Parasitic and Allergenic Products OVRR/CBER/FDA

2. Division Mission and Functions Assure safe and effective products for immunological control of bacterial, parasitic, and allergenic agents affecting human health

3. Examples of Possible New or Improved Products Respiratory Pathogens –Streptococcus pneumoniae –Mycobacterium tuberculosis –Pseudomonas aeruginosa –Neisseria meningitidis A,B,C,Y,W125 –Group B Streptococci –Bordetella pertussis –Chlamydia pneumoniae –Corynbacterium diphtheriae –Non-typeable H. influenzae –Moraxella catarrhalis Sexually Transmitted Pathogens –Neisseria gonorrheae –Chlamydia trachomatis Pathogens Encountered by Penetrating Inoculation –Borrelia burgdorfi –Plasmodium species –Leishmania species –Clostridium tetani –Staphylococcus aureus –Schistosoma species –Trypanosoma cruzi Special Pathogens (BT) –Bacillus anthracis –Clostridium botulinum –Franciscella tularensis –Yersinia pestis Scope of DBPAP Product Responsibilities

4. Examples of Possible New or Improved Products Diarrhea-Causing Pathogens –Enterotoxigenic E. coli –Shigella species –Vibrio cholerae –Campylobacter jejuni Other Mucosally-Trafficking Pathogens –Clostridium difficile –Salmonella typhi –Mycobacterium leprae –Helicobacter pylori –STEC and EPEC Allergenic Antigens –Latex –Cockroach –Short ragweed Skin Test Antigens –PPD –Coccidioidin –Leishmania Live Biotherapeutic Products –Lactobacillus –E. coli –Clostridia Scope of DBPAP Product Responsibilities

5. Division of Bacterial, Parasitic and Allergenic Products (DBPAP) Laboratory of Immunobiochemistry Jay Slater, M.D.-Chief Immediate Office of the Director Richard Walker, Ph.D.-Director Milan Blake, Ph.D.-Deputy Director Regulatory Staff Administrative Staff Laboratory of Methods Development and Quality Control Bruce Meade, Ph.D.-Chief Laboratory of Respiratory and Special Pathogens Drusilla Burns, Ph.D.-Chief Laboratory of Bacterial Polysaccharides Willie Vann, Ph.D.- Chief Laboratory of Enteric and Sexually Transmitted Diseases Dennis Kopecko, Ph.D.-Chief Laboratory of Mycobacterial Diseases and Cellular Immunology Sheldon Morris, Ph.D.-Chief

6. Division of Bacterial, Parasitic and Allergenic Products (DBPAP) 6 Laboratories (76 people) –13 Tenured Principal Investigators –7 Tenure-track investigators –43 Full-time equivalent staff –13 Contract staff (e.g., post-doctoral fellows)

7. Laboratory Mission and Functions Dependent on Researcher/Reviewers Conduct regulatory review Conduct critical research: programmatic and special task Serve outside organizations as recognized subject matter experts Find outside resources to support research Responsibilities of Researcher/Reviewers

8. Regulatory Review and Laboratory Work: A Synergistic Combination Provide reagents/standards Assay development Improved technology Trouble-shooting Gain expertise to: –Better anticipate issues/identify and fill knowledge gaps –Provide expert input to vaccine community –Provide guidance advice to industry

9. Laboratory of Respiratory and Special Pathogens Areas of Research Studies of Bordetella pertussis, Bacillus anthracis, C. diptheriae and C. botulinum and Yersinia spp. Characterization of Virulence Factors and Studies on Mechanism of Action Studies on Regulation of Gene Expression Animal Models of Infection Identification and characterization of iron-regulated virulence factors Mechanism of toxin entry into nerve cells, toxin interaction with cellular components, and toxin persistence

10. Product Research Laboratories Respond to Regulatory Needs Laboratory of Pertussis Established 19601980 2000 Whole Cell PertussisVaccine Regulatory-related studies (potency and other tests) Acellular Pertussis Vaccine Antigen identification Animal model development Clinical serology New product quality assays Bioterrorism Agents Included In Program LMDQC Lab Established Immune responses Product immunogenicity LRSP Lab Established Genetic manipulation of pathogens Toxin actions Application of the “Animal Rule”

11. Laboratory of Methods Development and Quality Control Research and Regulatory Activities  Develop and evaluate: –Quality control methods for bacterial vaccines –Assay methods for immune response measurement –Animal models Bioassays for potency and toxicity  Members are testing specialists Activities not restricted to single product area

12. Recent Projects Anthrax Vaccine –Evaluation and optimization of immunoassay methods for use in clinical evaluation or in animal models that support the “Animal Rule” –Anthrax Vaccine Potency Test Development Mouse immunogenicity model Anthrax vaccine reference materials development Pertussis Vaccine –Serologic diagnosis of pertussis in adults and adolescents Development and evaluation of simple, easily transferable immunoassay for IgG anti-PT (CDC/CBER collaboration) Diphtheria Vaccine –International collaborations to evaluate alternative (non-lethal) animal tests for diphtheria potency

13. LABORATORY OF BACTERIAL POLYSACCHARIDES Areas of Research Characterization of polysaccharide conjugate vaccines Conformation of polysaccharide antigens Biosynthesis of capsular polysaccharides Role of Neisseria outer membrane proteins in disease Interaction of polysaccharides with the immune system Neisseria Oligosaccharide antigen

14. LABORATORY OF BACTERIAL POLYSACCHARIDES (con’t) Highlights 2002-2006 Developed DNA based method for serotyping pathogenic Neisseria Applied new NMR methods to analysis of carbohydrate conformation Developed methodology for Meningococcal Group A Vaccine

15. Novel Vaccine Technologies and Vaccination Strategies Mortality in the “Meningitis belt” of Africa CBER’s unique conjugation technology for Meningococcal Vaccines transferred to MVP. Outcome: newly licensed meningococcal conjugate vaccines

16. The Laboratory of Mycobacterial Diseases and Cellular Immunology Areas of Research Evaluation of protective innate and adaptive immune responses to intracellular bacteria Assessment of live attenuated TB vaccine strains and DNA vaccination strategies against tuberculosis Characterization of a unique family of tuberculosis proteins

17.  5 new TB vaccines now in clinical trials  Can they be used safely in individuals previously infected with Mtb? “Koch Response ” Vaccine Mtb Infected Worsening Disease In Vitro Assays to Predict the Safety of TB Vaccines CBER Labs, in collaboration with AERAS Global TB Foundation, developing a preclinical post-infection animal model assay to evaluate safe use of new TB vaccines in infected individuals.

18. Laboratory of Immunobiochemistry Cockroach allergen standardization Microarray method for potency determinations Determination of optimal surrogate test Depletion analysis of CR extracts MDR proteins in T cell activation Allergen structure and function Modifying allergic responses Extract potency determinations Regulation of T cell responses by RSV Endotoxins and  -glucans in allergen extracts

19. Laboratory of Enteric and Sexually Transmitted Diseases Areas of Research Invasion mechanisms of enteric pathogens Genetic regulation of bacterial virulence genes Mucosal immunity, dosing and adjuvants Anthrax and Shigella - Genetic analysis and development of live attenuated Salmonella- vectored vaccines

20. Anthrax PA Delivered by a Live-Attenuated Vaccine Platform (Ty21a) Protects Mice from a Lethal Spore Challenge Dose #1 5x10 7 cells A/J mice immunized via i.p. or i.n. routes with Ty21a or Ty21a-PA 0Week 2Week 4Week 7 Dose #2Dose #3Challenged with 10 6 aerosolized Stern spores

21. Communication within DBPAP Laboratory meetings Work in Progress Review of manuscripts DBPAP Update

23. THE OFFICE OF VACCINES THANKS YOU FOR HELPING US BETTER SERVE THE PUBLIC HEALTH