Division of Bacterial, Parasitic and Allergenic Products Jay E. Slater, MD Director, DBPAP 28 February 2012

2/19 Office of Vaccines Research and Review Director Marion Gruber, Ph.D. (acting) Deputy Director Philip Krause, M.D. (acting) Associate Director for Research Konstantin Chumakov, Ph.D. Associate Director for Medical Policy and Vaccine Safety Karen Farizo, M.D. (acting) Associate Director For Management and Scientific Affairs Erik Henchal, Ph.D. Associate Director for Regulatory Policy Theresa Finn, Ph.D. Division of Bacterial, Parasitic and Allergenic Products Director: Jay Slater, M.D. Deputy: Drusilla Burns, Ph.D. Division of Bacterial, Parasitic and Allergenic Products Director: Jay Slater, M.D. Deputy: Drusilla Burns, Ph.D. Division of Viral Products Director: Jerry Weir, Ph.D. Deputy: Robin Levis, Ph.D. Division of Viral Products Director: Jerry Weir, Ph.D. Deputy: Robin Levis, Ph.D. Division of Vaccines and Related Products Applications Director: Wellington Sun, Ph.D. Deputy: Loris McVittie, Ph.D. Division of Vaccines and Related Products Applications Director: Wellington Sun, Ph.D. Deputy: Loris McVittie, Ph.D.

3/19 OVRR research is conducted in three major areas with special emphasis on products of high public health importance and visibility Safety To study factors affecting safety of regulated products, create and validate appropriate methods and standards Efficacy To study biomarkers and introduce new methods and standards to evaluate and improve vaccine efficacy Availability To develop new concepts and methods opening novel regulatory pathways to improve availability of vaccines and related products

4/19 Safety  Evaluate purity of components used in manufacture of vaccines, including cell substrates, and develop methods for detection of adventitious agents  Study the utility of novel scientific technologies based on genomics, proteomics, etc., for comprehensive evaluation of vaccines and related products and ensuring their consistency  Create methods and models to study potential toxic effects of vaccine antigens, adjuvants, and other components of vaccines  Determine biomarkers of pathogenicity and develop new methods to evaluate and ensure safety of live vaccines and related products  Study the mechanisms of vaccine-related adverse events, ways to mitigate them, and biomarkers of predisposition

5/19 Efficacy  Study pathogenesis to identify correlates of protection and biomarkers of vaccine efficacy, including studies in special populations  Create methods for evaluation and improvement of immunogenicity, potency, and protectivity of vaccines  Study the mechanisms of innate and adaptive immunity against viral and bacterial diseases and mechanisms of immunopathology, including allergy  Study the mechanism of action of adjuvants and create methods for predicting their effectiveness

6/19 Availability  Create new approaches to inducing protective immunity, including synthetic and DNA vaccines, modifications of antigen presentation and vaccine delivery routes  Create and evaluate methods for monitoring and controlling the manufacturing process  Evaluate novel scientific technologies for manufacture of vaccines, including use of novel cell substrates, plants, and other innovative platforms  Create methods for evaluation of vaccines that lead to refinement, reduction, and replacement of tests in laboratory animals  Conduct studies to facilitate the development and regulation of probiotics for preventive and therapeutic use

7/19 Division of Bacterial, Parasitic and Allergenic Products (DBPAP) Merger (1999) of Division of Bacterial Products (DBP) and Division of Allergenic Products and Parasitology (DAPP) Leadership Drusilla Burns, PhD (Acting) Richard Walker, PhD Milan Blake, PhD Jay Slater, MD 2010-present

8/19 Division of Bacterial, Parasitic and Allergenic Products (DBPAP) Immediate Office of the Director Jay Slater, MD – Director Drusilla Burns, PhD – Deputy Director 8 FTE Laboratory of Respiratory and Special Pathogens Michael Schmitt, PhD – Chief (Acting) Juan Arciniega, D Sci Drusilla Burns, PhD James Keller, PhD Tod Merkel, PhD 16 FTE, 8 ORISE Laboratory of Bacterial Polysaccharides Willie Vann, PhD – Chief Mustafa Akkoyunlu, PhD Margaret Bash, MD Wei Wang, PhD John Cipollo, PhD Daron Freedberg, PhD 18 FTE, 10 ORISE Laboratory of Enteric and Sexually Transmitted Diseases Scott Stibitz, Ph.D. – Chief Dennis Kopecko, PhD 8 FTE, 9 ORISE Laboratory of Mycobacterial Diseases & Cellular Immunology Sheldon Morris, Ph.D. – Chief Siobhán Cowley, PhD Karen Elkins, PhD 10 FTE, 6 ORISE As of 26 October 2011 Laboratory of Immunobiochemisty Ron Rabin, M.D. – Chief Jay E. Slater, MD 9 FTE, 6 ORISE

9/19 DBPAP regulatory/research portfolio Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium diphtheriae Invasive, protective responses to polysaccharides Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Intracellular (Francisella tularensis) Mycobacterium tuberculosis Mycobacterium bovis Enteric (Campylobacter jejuni) Salmonella typhi (Salmonella typhimurium) (Shigella dysenteriae) Parasite (Plasmodium spp) Other/emerging (Yersinia pestis) (Staphylococcus aureus) Allergenic products (Probiotics)

10/19 DBPAP regulatory/research portfolio Bacterial Polysaccharides (LBP) Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium diphtheriae Invasive, protective responses to polysaccharides Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Intracellular (Francisella tularensis) Mycobacterium tuberculosis Mycobacterium bovis Enteric (Campylobacter jejuni) Salmonella typhi (Salmonella typhimurium) (Shigella dysenteriae) Parasite (Plasmodium spp) Other/emerging (Yersinia pestis) (Staphylococcus aureus) Allergenic products (Probiotics)

11/19 Bacterial polysaccharides (LBP) Akkoyunlu Regulation of humoral immune response against polysaccharide vaccines by bacterial products Bash To present protein targets as alternatives based on molecular epidemiology of the pathogen where polysaccharide vaccines have lacked success Cipollo Mass spectrometry of carbohydrates as a tool for characterization of bacterial vaccines and pathogens Freedberg Improvement of biological product quality by application of new technologies to characterize of vaccines and blood products: NMR spectroscopy and light scattering Vann To detemine the metabolic pathway for the synthesis of polysaccharides in gram negative pathogens and to use this knowledge to development methods for preparing glycoconjugate vaccines using metabolic engineering To improve and understand the manufacture of current conjugate vaccines through the investigation of conjugation chemistry Wang To investigate the genetics of pathogenesis of gram negative bacteria. M. catarrhalis is a model organism for these studies. To study the regulation of M. catarrhalis virulence gene expression and identify biomarkers for developing vaccine against M. catarrhalis.

12/19 DBPAP regulatory/research portfolio Enteric and Sexually Transmitted Diseases (LESTD) Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium diphtheriae Invasive, protective responses to polysaccharides Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Intracellular (Francisella tularensis) Mycobacterium tuberculosis Mycobacterium bovis Enteric (Campylobacter jejuni) Salmonella typhi (Salmonella typhimurium) (Shigella dysenteriae) Parasite (Plasmodium spp) Other/emerging (Yersinia pestis) (Staphylococcus aureus) Allergenic products (Probiotics)

13/19 Enteric and Sexually Transmitted Diseases (LESTD) Stibitz Molecular genetics of virulence and virulence-gene regulation in bacterial respiratory pathogens Kopecko Evaluate safety and utility of Salmonella typhi Ty21a as an oral vaccine delivery platform for expression of foreign antigens and delivery of anti-cancer therapies Analyze pathogenesis of and immune responses to Campylobacter jejuni infection in humans Evaluate the vaccine potential of inactivated enteric bacteria

14/19 DBPAP regulatory/research portfolio Immunobiochemistry (LIB) Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium diphtheriae Invasive, protective responses to polysaccharides Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Intracellular (Francisella tularensis) Mycobacterium tuberculosis Mycobacterium bovis Enteric (Campylobacter jejuni) Salmonella typhi (Salmonella typhimurium) (Shigella dysenteriae) Parasite (Plasmodium spp) Other/emerging (Yersinia pestis) (Staphylococcus aureus) Allergenic products (Probiotics)

15/19 Immunobiochemistry (LIB) Rabin IFN-  isoforms that mediate immunosuppression induced by the respiratory syncytial virus Slater Development and validation of a multiplex allergen extract potency assay Endotoxins in allergen extracts

16/19 DBPAP regulatory/research portfolio Mycobacterial Diseases and Cellular Immunology (LMDCI) Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium diphtheriae Invasive, protective responses to polysaccharides Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Intracellular (Francisella tularensis) Mycobacterium tuberculosis Mycobacterium bovis Enteric (Campylobacter jejuni) Salmonella typhi (Salmonella typhimurium) (Shigella dysenteriae) Parasite (Plasmodium spp) Other/emerging (Yersinia pestis) (Staphylococcus aureus) Allergenic products (Probiotics)

17/19 DBPAP regulatory/research portfolio Respiratory and Special Pathogens (LRSP) Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium diphtheriae Invasive, protective responses to polysaccharides Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae Intracellular (Francisella tularensis) Mycobacterium tuberculosis Mycobacterium bovis Enteric (Campylobacter jejuni) Salmonella typhi (Salmonella typhimurium) (Shigella dysenteriae) Parasite (Plasmodium spp) Other/emerging (Yersinia pestis) (Staphylococcus aureus) Allergenic products (Probiotics)

18/19 Respiratory and Special Pathogens (LRSP) Arciniega Development and refinement of potency and toxicity tests for bacterial vaccines Burns Bacterial toxin structure/function relationships Study of host response to immunization with anthrax and Staphylococcal aureus vaccines Keller Clostridial neurotoxin vaccine and antitoxin research Merkel Development of animal aerosol challenge models for pertussis, anthrax and disease caused by Staphylococcus aureus. Analysis of gene regulation in Bordetella pertussis Schmitt Characterization of iron transport systems of Corynebacterium diphtheriae Analysis of gene regulation in C. diphtheriae

19/19 LMDCI presenters, 28 Oct 2011 Sheldon Morris, PhD, Laboratory Chief (PI) Miranda Oakley, PhD, Staff Fellow Karen Elkins, PhD, Supervisory Research Biologist (PI) Roberto De Pascalis, MD, Visiting Associate Siobhán Cowley, PhD, Visiting Scientist (PI)