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

Division of Bacterial, Parasitic and Allergenic Products

Jay E. Slater, MDDirector, DBPAP28 February 2012

2/19

Office of Vaccines Research and Review

Office of Vaccines Research and ReviewDirector

Marion Gruber, Ph.D. (acting)Deputy Director

Philip Krause, M.D. (acting)

Associate Director for ResearchKonstantin 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 Directorfor Regulatory PolicyTheresa Finn, Ph.D.


Director: Jay Slater, M.D. Deputy: Drusilla Burns, Ph.D.


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.

3/19

OVRR research is conducted in three major areas with special emphasis on products of high public health importance and visibility

SafetyTo study factors affecting safety of regulated

products, create and validate appropriate methods and standards

EfficacyTo 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) 1999-2000 Richard Walker, PhD 2000-2008 Milan Blake, PhD 2008-2010 Jay Slater, MD 2010-present

8/19

Division of Bacterial, Parasitic and Allergenic Products (DBPAP)Division of Bacterial, Parasitic and Allergenic Products (DBPAP) Immediate Office of the Director

Jay Slater, MD – DirectorDrusilla Burns, PhD – Deputy Director

8 FTE

Laboratory of Respiratory and Special Pathogens

Michael Schmitt, PhD – Chief (Acting)Juan Arciniega, D SciDrusilla Burns, PhDJames Keller, PhDTod Merkel, PhD16 FTE, 8 ORISE

Laboratory of BacterialPolysaccharides

Willie Vann, PhD – ChiefMustafa Akkoyunlu, PhD

Margaret Bash, MDWei Wang, PhD

John Cipollo, PhDDaron Freedberg, PhD

18 FTE, 10 ORISE

Laboratory of Enteric and Sexually Transmitted Diseases

Scott Stibitz, Ph.D. – ChiefDennis Kopecko, PhD

8 FTE, 9 ORISE

Laboratory of Mycobacterial Diseases & Cellular Immunology

Sheldon Morris, Ph.D. – ChiefSiobhán Cowley, PhD

Karen Elkins, PhD10 FTE, 6 ORISE

As of 26 October 2011

Laboratory of Immunobiochemisty

Ron Rabin, M.D. – ChiefJay E. Slater, MD9 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


Bacterial Polysaccharides (LBP)








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


Enteric and Sexually Transmitted Diseases (LESTD)








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


Immunobiochemistry (LIB)








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


Mycobacterial Diseases and Cellular Immunology (LMDCI)








17/19


Respiratory and Special Pathogens (LRSP)

Non-invasive, toxin producers Bacillus anthracis (Bordetella parapertussis) Bordetella pertussis (Clostridium botulinum) Clostridium tetani Corynebacterium

diphtheriae







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)

Documents

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