LIB site visit January 24, 2002

1
LIB site visitJanuary 24, 2002

• Jay E. Slater, MD
• Laboratory of Immunobiochemistry
• FDA/CBER/OVRR/DBPAP

2
History of LIB

• Laboratory of Allergenic Products, Division of
  Bacterial Products
• Laboratory of Immunobiochemistry, Division of
  Allergenic Products and Parasitology
• Allergenic Products Testing Lab
• Allergenic Products Research Lab
• Laboratory of Immunobiochemistry, Division of
  Bacterial Parasitic and Allergenic Products

3
LIB mission

• LIB supports the regulatory mission of CBER and
  FDA in assuring the safety and efficacy of
  allergenic products in the US by
• 1. performing original research in the fields of
  allergen structure and function, and
  immunomodulation
• 2. responding to specific regulatory needs with
  directed research projects 
• 3. providing expert advice and support for CBER
  and FDA staff regarding allergy and allergenic
  products
• 4. reviewing, confirming and approving lot
  release data from allergenic product
  manufacturers
• 5. assisting in the review of BLAs and INDs that
  relate to allergenic products

4
LIB is in NIH, Building 29, in the basement and
on the 2nd floor
211
214-218
212
203
B3
B1
5
Equipment

• tissue culture hoods
• chemical hoods
• centrifuges
• CO2 incubators
• light microscopes
• thermocyclers
• vertical and horizontal electrophoresis
  apparatuses and power sources
• UV and light spectrophotometers
• balances
• pH meters

6
More equipment

• mouse plethysmograph
• fluorescent imager
• magnetic cell sorter
• flow cytometer (room 513)

7
Core facilities (Buildings 29, 29A and Nicholson
Lane)

• DNA sequencing
• oligonucleotide primer synthesis
• peptide synthesis
• N-terminal sequencing
• mass spectrometry analysis
• amino acid composition
• lyophilization

8
Shared equipment

• gene expression microarray
• circular dichroism spectrometer (Building 5)
• NMR spectrometers (300 MHz and 500 MHz 700 MHz
  on order)

9
Scientific goals

• Allergen structure and function
• Immunomodulation of allergic responses
• Preparation and preservation of reference
  standards

10
Scientific goals
Allergen structure and function
Cross-reactivity between foods and latex
Precipitates in allergen extracts
Latex, cockroach, hymenoptera
MALDI-TOF of allergen extracts
RSV, MDR
Extract preservation and potency determinations
Modifying allergic responses
LPS
Lyophilization
SELDI technology in identification of allergens
PAR-2 activation in mast cells
11
Scientific goals
Allergen structure and function
Latex, cockroach, hymenoptera
RSV, MDR
Extract preservation and potency determinations
Modifying allergic responses
LPS
12
Scientific goals
Allergen structure and function
Latex, cockroach, hymenoptera
RSV, MDR
Extract preservation and potency determinations
Modifying allergic responses
LPS
13
LIB research program
Research Regulatory
Latex, cockroach, hymenoptera Regulation of recombinant allergens immunotherapy options
LPS Adjuvant safety and efficacy
Extract potency determination methods Lot release for current and future products
Extract preservation US standard reference maintenance
RSV Parameters of effective immunomodulation
MDR Novel approaches to immunotherapy
14
Technical capabilities
Project Primary tools and capabilities
latex hymenoptera protein analysis DNA amplification/analysis cloning and mutagenesis
cockroach combinatorial IgE library
LPS plethysmography
RSV MDR flow cytometry cell sorting
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LIB technicians are involved in research and
regulation
Position Research activity
Marc Alston Biologist RSV, lyophilization
Mona Febus Microbiologist hymenoptera
Albert Gam Biologist hymenoptera
Melissa Patterson Biologist latex, cockroach, precipitates
Cherry Valerio Biologist LPS, lyophilization
16
Rabin presentations

• Characterization of responses to RSV by T-cells
  from human tonsil (Rabin and Alston)
• Modification of multidrug resistance protein
  activity as a potential mechanism of
  immunomodulation (Rabin and Huang)

17
Soldatova presentations

• Glycosylation and the allergenicity of honeybee
  venom hyaluronidase (Soldatova, Gam and
  Dobrovolskaia)
• Cloning of a new bee venom allergen, acid
  phosphatase (Soldatova and Dobrovolskaia)

18
Slater presentations

• The effects of LPS on allergen responses (Slater,
  Valerio and Trivedi)
• Modification of the latex allergen Hev b 5 for
  the immunotherapy of latex allergy (Slater and
  Patterson)
• Molecular characterization of the immune response
  to cockroach allergens (Finlay, Slater and
  Patterson)