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Laboratory of Immunobiochemistry. Allergenic Products Advisory Committee, April 8, 2003. Allergenic Products Advisory Committee, April 8, 2003. Lab overview Staffing Lot release Reference replacement Operational issues Sheep serum replacement issues ISO certification report

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Laboratory of immunobiochemistry l.jpg

Laboratory of Immunobiochemistry

Allergenic Products Advisory Committee, April 8, 2003


Allergenic products advisory committee april 8 2003 l.jpg
Allergenic Products Advisory Committee, April 8, 2003

  • Lab overview

    • Staffing

    • Lot release

    • Reference replacement

  • Operational issues

    • Sheep serum replacement issues

    • ISO certification report

  • Research/regulatory update

    • Endotoxin studies

    • Cockroach antigens and antibodies


Lab overview l.jpg
Lab overview

  • Staffing

  • Lot release

  • Reference replacement


Slide4 l.jpg

  • Principal Investigators

    • Jay E. Slater, MD, Lab Chief – Supervisory Medical Officer (4)

    • Ronald Rabin, MD - Senior Staff Fellow (2)

  • Post Doctoral Fellows

    • Jonny Finlay, PhD - IRTA (2)

    • Bo Chi, MD - Visiting Associate (<1)


Slide5 l.jpg

  • Research Technicians

    • Albert Gam – Biologist (2)

    • Mona Febus – Microbiologist (3)

    • Marc Alston – Biologist (2)

    • Cherry Valerio – Biologist (2)

    • Katia Dobrovolskaia – Visiting associate (2)



Routine regulatory activities l.jpg
Routine” regulatory activities

  • Lot release

  • Reference distribution

  • Reference maintenance

    • semiannual checks

    • replacement


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  • Lot release activities

    • 357 protocols submitted and reviewed

    • 1 withdrawn

  • Reference distribution

    • 2002: 1978 vials in 107 shipments sent to manufacturers





Operational issues l.jpg
Operational issues

  • Replacement of cat and ragweed antisera

  • Transition to ISO compliance


Ragweed and cat antisera need to be replaced l.jpg
Ragweed and cat antisera need to be replaced

  • S2a cat

    • Released in 1998

  • S6 ragweed

    • Released in 2000

  • Replacement programs for both initiated spring 2002



Immunization protocol15 l.jpg
Immunization protocol

Immunization doses

plasmapheresis


Transmissible spongiform encephalopathies l.jpg
Transmissible spongiform encephalopathies

  • Animal

    • scrapie (sheep and goats)

    • chronic wasting disease (mule deer, elk)

    • transmissible mink encephalopathy

    • bovine spongiform encephalopathy

      • feline spongiform encephalopathy


Transmissible spongiform encephalopathies19 l.jpg
Transmissible spongiform encephalopathies

  • Human

    • kuru

    • Creutzfeldt-Jakob disease

      • classic sporadic

      • familial

      • iatrogenic

      • new variant (a/w bovine TSE)

    • Gerstmann-Sträussler-Scheincker

    • fatal familial insomnia

    • sporadic fatal insomnia


Scrapie l.jpg
Scrapie

  • In Europe for >250 years

  • In US since 1947

    >1000 flocks

  • Vertical transmission

  • Horizontal transmission, presumably by contamination with placenta and blood during lambing season

  • Long incubation period

  • No human transmission


Slide21 l.jpg


Scrapie eradication program l.jpg
Scrapie eradication program especially at codon 171

  • Preclinical testing and surveillance

    • Live animal test (third eyelid biopsy)

      • May take months to years to turn positive

  • Tracking of infected and exposed animals

  • Cleanup strategies: identify and genotype exposed animals

    • Destroy QQ exposed

    • QR or RR exposed are tracked but may be slaughtered for human consumption


Slide23 l.jpg

  • Not believed to pose any risk to humans especially at codon 171

    • No recognized human transmission in three centuries of exposure in Europe

  • This serum is safe to use because

    • No documented transmission to humans

    • Contact with affected sheep was limited

      • Not in adjoining pens; >30 feet distant

    • Normal BSL 2 precautions in place for all work with animal sera

  • However, in order to maintain a serum reagent that is as safe as possible…


Current approach l.jpg
Current approach especially at codon 171…

  • Begin immunizing two new sheep

  • Process plasma from ewes 6747 and 7777 now

  • Conserve current stocks


Current approach25 l.jpg
Current approach especially at codon 171…

  • If new sera are available before we run out, sera from 6747 and 7777 will be saved frozen for possible future use

  • If we have a shortfall, sera from 6747 and/or 7777 will be used until the new sera are available


Current approach26 l.jpg
Current approach especially at codon 171…

  • Advantages

    • Highest degree of safety

    • Large supplies for future

  • Disadvantages

    • Possibility of two serum switches in short period

    • Time

    • Expense


Slide28 l.jpg

CBER Laboratory Quality Management Initiative especially at codon 171

  • Seek ISO-17025 compliance for official product testing

    • ISO – International Organization for Standardization, Geneva, Switzerland

    • 17025: “General requirements for the competence of testing and calibration laboratories” (1999)

      • Set of guidelines for labs that do testing and calibration to show operation of a quality system to assure technical competence and production of valid results


Cber laboratory quality management initiative l.jpg
CBER Laboratory Quality Management Initiative especially at codon 171

  • Establish policy with Center level Quality Manual

  • Audit for compliance with ISO-17025

  • Obtain Test/Lab Accreditation where appropriate

    • “Accreditation – successful 3rd party audit


Why is cber becoming iso compliant l.jpg
Why is CBER becoming ISO compliant? especially at codon 171

  • Establish recognized competence, assure the trust and value of our data and processes

  • We require the manufacturers’ labs to be in GMP compliance

    • International efforts at harmonization are attempting to equate GMP and ISO requirements

  • ISO is an internationally recognized standard


Why is cber becoming iso compliant continued l.jpg
Why is CBER becoming ISO compliant? (continued) especially at codon 171

  • Implement Laboratory Quality Management policies and practices for official testing activities

    • To document a high level of training, competence, and proficiency

    • To establish a consistent product testing process


Elements of iso compliance l.jpg
Elements of ISO compliance especially at codon 171

  • Management of

    • People

    • Equipment

    • Documents

    • Processes


Elements of iso compliance33 l.jpg
Elements of ISO compliance especially at codon 171

  • Management of People

    • Defined roles

    • Appropriate training

    • Demonstrated proficiency

      • Initial and ongoing

    • Authorization process


Elements of iso compliance34 l.jpg
Elements of ISO compliance especially at codon 171

  • Management of Equipment

    • Program for equipment calibration

    • Maintenance

    • Process to assure that only calibrated and maintained equipment is used

    • Assurance of measurement traceability to accepted standards


Elements of iso compliance35 l.jpg
Elements of ISO compliance especially at codon 171

  • Management of Documents

    • Includes policies, procedures, specifications, equipment manuals, certifications

    • Must be reviewed, issued and controlled

    • Approved and issued prior to use


Elements of iso compliance36 l.jpg
Elements of ISO compliance especially at codon 171

  • Management of Processes

    • Approval of testing materials

    • Environmental specifications and monitoring

    • Handling of samples

    • Validation and suitability

    • Handling of data (including non-conforming data)

    • Corrective action, Preventive action systems

    • Internal Audits

    • Management review

    • Recording and handling complaints


Cber s commitment to implementation of a lab quality system l.jpg
CBER especially at codon 171’s commitment to implementation of a Lab Quality System

  • Establishment of CBER Quality Board

  • Development of Quality Assurance structure within CBER

    • Appointment of Center Level Quality Manager

    • Hiring Office quality Managers

    • Appointment and hiring of Division Quality Coordinators

  • Preparation of CBER Quality Manual

  • Purchase of Integrated Quality Management computer software


What will this mean to lib l.jpg
What will this mean to LIB? especially at codon 171

  • No substantive protocol revisions

  • Documentation

    • Formatting

    • Substance

  • Formal separation of research and regulatory equipment

  • Internal audits

  • External audits


Timetable tentative l.jpg
Timetable (tentative) especially at codon 171

  • Implementation in stages over the next 3 years… Seek accreditation in 2005

    • Software operational during 2003

    • Policies and Quality Manual issued 2003

    • Initiation of compliance audits (ongoing)

    • Training and process development (ongoing)


Laboratory of immunobiochemistry40 l.jpg

Laboratory of Immunobiochemistry especially at codon 171

Research/regulatory update


Active research projects l.jpg
Active research projects especially at codon 171

  • PI Slater

    • Cockroach allergen standardization

      • Determination of optimal surrogate test

      • Depletion analysis of CR extracts

    • Cockroach IgE combinatorial library

    • Endotoxin in allergen vaccines

  • PI Rabin

    • MDR proteins in T cell activation

    • RSV responses in human tonsil


Publications l.jpg
Publications especially at codon 171

Patterson ML, Slater JE. Characterization and comparison of commercially available German and American cockroach allergen vaccines. Clin Exp Allergy 2002;32:721-727

Sutherland MF, Drew A, Rolland JM, Slater JE, Suphioglu C, O'Hehir RE. Specific monoclonal antibodies and human IgE show Hev b 5 is an abundant allergen in high protein powdered latex gloves. Clin Exp Allergy 2002;32:583-589

Trivedi B, Valerio C,Slater JE. Endotoxin content of standardized allergen vaccines. J Allergy Clin Immunol 2003 (in press).


Publications reviews l.jpg
Publications (reviews) especially at codon 171

Lockey RF, Slater JE, Esch R. Preparation and standardization of allergen vaccines. In Middleton’s Allergy: Principles and Practice, 6th ed. St. Louis: Mosby (in press).


Abstracts l.jpg
Abstracts especially at codon 171

Rabin RL, Alston MA, Huang H, Slater JE. Cytokine secretion by activated T cells is dependent on multidrug resistance protein-1 (MRP-1). J Allergy Clin Immunol 2003; 111:S153.

Valerio C, Slater JE. The effects of lipopolysaccharide (LPS) on immune responses in C57Bl/6 mice. J Allergy Clin Immunol 2003; 111:S166.

Slater JE, Valerio C, Trivedi B. Endotoxin in standardized allergen vaccines. J Allergy Clin Immunol 2003; 111:S243.

Finlay WJJ, Rabin RL, Slater JE. Analysis of IgE heavy chain V-gene usage in human tonsil. J Allergy Clin Immunol 2003; 111:S313.


Endotoxin content of allergen vaccines l.jpg
Endotoxin content of allergen vaccines especially at codon 171

  • Allergenic extracts are not required to undergo evaluation for the presence of pyrogens (21CFR 610.13(b))

  • Prior studies confirmed variable endotoxin content (Siraganian, et al. J Allergy Clin Immunol 1979; 64:526-533)


Products exempted in 21 cfr 610 13 b l.jpg
Products exempted in 21 CFR 610.13(b) especially at codon 171

  • Blood products

  • Horse serum

  • Bacterial, rickettsial and viral vaccines

  • Toxoids

  • Toxins

  • Allergenic extracts


Lal gel clot method l.jpg
LAL gel-clot method especially at codon 171


Lal gel clot method48 l.jpg
LAL gel-clot method especially at codon 171


Endotoxin l.jpg
ENDOTOXIN especially at codon 171

(1,3) b–D- glucan

Factor C

Act. factor C

Factor B

Act. factor B

Act. factor G

Factor G

Proclotting enzyme

Clotting enzyme

Coagulogen

Coagulin


Endotoxin content of allergen vaccines possible interference l.jpg
Endotoxin content of allergen vaccines especially at codon 171– possible interference

  • Non-endotoxin (1,3)--D-glucans may induce clotting by an alternative pathway in the standard LAL assays

  • Proteases (especially in cat and mite extracts) may also induce clotting


Endotoxin content of allergen vaccines approach l.jpg
Endotoxin content of allergen vaccines - approach especially at codon 171

  • Determine endotoxin content using gel-clot method

  • Assess the contribution of non-endotoxin components ((1,3)--D-glucans, enzymes)


Study design l.jpg
Study design especially at codon 171

  • Standardized allergen vaccines

  • LAL gel-clot assay

  • Adsorption of selected allergens with ENP-silica resin, followed by LAL assay

    • Endotoxin neutralizing protein (ENP) is a ~12 kDa, cationic, amphipathic protein that binds to and neutralizes the biological activity of lipopolysaccharide.

  • Pre-treat selected allergens at 95°C for 15 min, followed by LAL assay


Slide53 l.jpg

G especially at codon 171

G

G

G

G

G

G

G

G

G

G

G

G

G

GP

GP

GP

GP

GP

GP

GP

GP

GP

P


Slide54 l.jpg

P especially at codon 171

P

P

G

G

G

G

G

GP


Slide55 l.jpg

G especially at codon 171

G

G

G

G

G

G

GP

GP


Slide56 l.jpg

G especially at codon 171

G

G

G

G

G

G

G

G

G

G

G

GP

GP


Heat inactivation l.jpg
Heat inactivation especially at codon 171


Conclusions l.jpg
Conclusions especially at codon 171

  • The observed LAL gel-clot activity probably represents real endotoxin content, not -glucan or protease activity


Is this amount of endotoxin physiologically significant l.jpg
Is this amount of endotoxin physiologically significant? especially at codon 171

  • Mean endotoxin content: 1,900 EU/mL (allergen immunotherapy dose 0.5 – 2.0 mL per month)

    • 40 – 50 EU/kg (2,800 to 3,500 EU) (administered IV) can elicit a rise in temperature, heart rate, and white blood cell count

Wolff SM. J Infect Dis 1973; 128:Suppl-64.

Michie HR, et al. N Engl J Med 1988 Jun 9 318;1481-6.


Specific endotoxin limits l.jpg
Specific endotoxin limits especially at codon 171

  • Product-specific

  • Generally based on

    • Drug dose

    • 5.0 EU/kg limit


Specific endotoxin limits64 l.jpg
Specific endotoxin limits especially at codon 171

* Based on USP limits and estimated maximum therapeutic doses


The clinical consequences of endotoxin in allergen vaccines have not been studied l.jpg
The clinical consequences of endotoxin in allergen vaccines have not been studied

  • No data that adverse events from IT are associated with endotoxin levels

  • No data to support a beneficial effect of endotoxins

  • Future studies of allergen IT should be controlled for endotoxin dose

  • Role of endotoxin in safety and efficacy of IT should be assessed


Conclusions66 l.jpg
Conclusions have not been studied

  • Pollens < cat and mite

  • Cat hair < cat pelt

  • D. pteronyssinus << D. farinae

    • Bioburden?

    • Endogenous heat-stable ENP-binding LAL activator in D. farinae?

    • Endogenous ENP in D. pteronyssinus?


Slide67 l.jpg
Plan have not been studied

  • Expand study of endotoxin content

    • Additional standardized and non-standardized extracts

    • Different methods (GC mass spec)

  • Investigate differences between D. farinae and D. pteronyssinus


Cockroach allergen standardization l.jpg
Cockroach allergen standardization have not been studied

  • Clinical studies

  • Developing the appropriate surrogate

    • Correlation

    • Depletion studies

  • IgE combinatorial library to cockroach


Cockroach allergen standardization69 l.jpg
Cockroach allergen standardization have not been studied

  • Clinical studies

  • Developing the appropriate surrogate

    • Correlation

    • Depletion studies

  • IgE combinatorial library to cockroach


Cockroach allergen standardization70 l.jpg
Cockroach allergen standardization have not been studied

  • Clinical studies

  • Developing the appropriate surrogate

    • Correlation

    • Depletion studies

  • IgE combinatorial library to cockroach


Current standardized allergens l.jpg

D. farinae have not been studied

D. pteronyssinus

Cat hair

Cat pelt

Short ragweed pollen

Hymenoptera

Honey bee

Wasp

Yellow jacket

Yellow hornet

White-faced hornet

Mixed vespid

Grass pollens

Bermuda grass

Red top

June (Kentucky blue)

Perennial rye

Orchard

Timothy

Meadow fescue

Sweet vernal

Current standardized allergens


Allergen standardization l.jpg
Allergen standardization have not been studied

  • Establish a US standard, and

  • Establish a testing procedure

    • Manufacturers may use the established procedure, or may develop equivalent procedures


Which allergens should be standardized impact criteria l.jpg
Which allergens should be standardized? Impact criteria have not been studied…

  • Availability of stable, preferably lyophilized material for use as long-term reference extracts.

  • Consistency of currently marketed product.

  • Widespread use as a diagnostic and/or therapeutic reagent in the U.S.

  • Number of manufacturers producing the product.

  • Potential use in immunotherapy or diagnostics.

  • Public health impact of correct diagnosis and/or adequate treatment.


Allergens and asthma l.jpg
Allergens and asthma have not been studied

  • Indoor allergens

    • dust mites*

    • cat*

    • cockroach

    • molds

    • dog

  • Outdoor allergens

    • molds

      * = already standardized


Cockroaches l.jpg
Cockroaches have not been studied


Why is cockroach allergy important l.jpg
Why is cockroach allergy important? have not been studied

  • Ubiquitous

  • Difficult to control

  • Associated with asthma


Why is cockroach allergen standardization important l.jpg
Why is cockroach allergen standardization important? have not been studied

  • To the patient

    • More accurate diagnosis

    • Safer and more effective immunotherapy

  • To the physician/scientist

    • Better science (if you can’t measure it, you can’t study it…)

      • Pathophysiology

      • Epidemiology

      • Environmental control

  • To the FDA

    • Safer, more effective product


Phase i laboratory l.jpg
Phase I - Laboratory have not been studied

  • Develop/adapt methods for allergen determination

  • Compare allergen content of different lots


Goals l.jpg
Goals have not been studied

  • Determine consistency of available US products:

    • protein content

    • specific allergen content

    • overall allergenicity

  • Determine best lot release measures


Extracts used as reference l.jpg
Extracts used as reference have not been studied

  • E2-Cg and E2-Ca

  • Previously characterized

  • Limited skin test data

  • Lyophilized; available in large quantities


Cockroach extracts studied l.jpg
Cockroach extracts studied have not been studied

  • From all nine allergen extract manufacturers







Correlation of protein concentrations and elisa results l.jpg
Correlation of protein concentrations and ELISA results competition ELISA)

Protein concentration

Relative potency

R2 = 0.83

R2 = 0.92

R2 = 0.96

R2 = 0.92

R2 = 0.93

R2 = 0.92

Bla g 1 levels

Bla g 2 levels


Conclusions89 l.jpg
Conclusions competition ELISA)

  • Commercially available cockroach allergen extracts:

    • vary widely in protein content, Bla g 2 content, SDS-PAGE banding pattern, and overall allergenicity.

    • appear to be less potent and contain less Bla g 1 than the candidate reference extracts


Conclusions90 l.jpg
Conclusions competition ELISA)

  • Established that cockroach allergen vaccines need to be standardized


What we need now l.jpg
What we need now competition ELISA)…

  • New cockroach references

  • Characterize the references

  • ID50EAL testing (Intradermal Dilution for 50 mm Sum of Erythema Determines Bioequivalent Allergy Units)

  • Proceed to next phase


Phase ii clinical l.jpg
Phase II - Clinical competition ELISA)

  • skin testing, histamine release, IT data

  • establish biological unitage and ideal dosing ranges


Id 50 eal testing l.jpg
ID competition ELISA)50EAL testing

  • Proficiency

  • Recruitment

  • Testing

  • Analysis


Id 50 eal testing94 l.jpg
ID competition ELISA)50EAL testing


Recruitment l.jpg
Recruitment competition ELISA)

  • Inclusion criteria

    • 18 to 65 years of age

    • history of allergic disease, such as allergic rhinitis, related to exposure to the allergen of interest

    • puncture sum of erythema diameter responses (ΣE) to the allergen concentrate of ≥30 mm.


Recruitment96 l.jpg
Recruitment competition ELISA)

  • Exclusion criteria

    • Asthma with use of systemic steroids in the past 12 months

    • Peak flow < 75% predicted at the time of testing

    • Skin coloring or condition that would preclude the measurement of erythema responses

    • Dermographism (> 4 mm ΣE following saline skin test)

    • Immunotherapy – past or present - with the test allergen

    • Current use of antihistamines, tricyclic antidepressants, MAO inhibitors, and beta-blockers


How many study subjects l.jpg
How many study subjects? competition ELISA)

Rabin et al., Sample Size Considerations for Establishing Clinical Bioequivalence of Allergen Formulations. Arb.Paul Ehrlich Inst.Bundesamt Sera Impfstoffe Frankf.A.M, in press


D for d50 should be 10 l.jpg
d competition ELISA)for D50 should be 10%

BAU/mL= 3-(14 - mean D50) * 100,000


For d50 is about 10 20 l.jpg
competition ELISA)for D50 is about 10-20%

Smith et al. Annals Allergy Asthma Immunol 1995; 75:317-323


For d50 is about 10 20100 l.jpg
competition ELISA)for D50 is about 10-20%


How many study subjects101 l.jpg
How many study subjects? competition ELISA)

  • Estimate n = 40 to establish D50 for each extract (based on /d = 1.5): 80

  • Geographic diversity: 80 x 3 = 240

  • Overlap between American CR and German CR allergic subjects may permit reduction in n (150-200)


Conclusions102 l.jpg
Conclusions competition ELISA)

  • Established that cockroach allergen vaccines need to be standardized

  • Need to establish the potency of candidate US reference materials by bioassay (ID50EAL)


Niaid inner city asthma consortium l.jpg
NIAID Inner City Asthma Consortium competition ELISA)

“…established in FY 2002 to explore and evaluate promising new strategies for the treatment of asthma among minority children residing in the inner city. This consortium of basic scientists and clinical investigators will conduct clinical studies to elucidate the immunopathogenesis and natural history of asthma in this population.”

From the FY 2003 Budget Justification Narrative, NIAID,

http://www.niaid.nih.gov/director/congress/2002/cj/narrative.htm


Niaid inner city asthma consortium steering committee l.jpg

Busse, William W., MD competition ELISA)Chair

Adams, Kenneth, PhD

Eggleston, Peyton A., MD

Gruchalla, Rebecca S., MD, PhD

Kattan, Meyer, MD

Kercsmar, Carolyn M., MD

Liu, Andrew H., MD

Malveaux, Floyd J., MD, PhD

Mitchell, Herman, PhD

Morgan, Wayne, MD, CM

O'Connor, George T., MD, MS

Pongracic, Jacqueline A., MD

Sampson, Hugh A., MD

Smartt, Ernestine, RN

Strunk, Robert C., MD

Szefler, Stanley J., MD

NIAID Inner City Asthma Consortium steering committee


Timetable l.jpg
Timetable competition ELISA)

  • Steering committee approval - done

  • Study centers identified

  • Order extracts

  • IRB approvals

  • IND approval

  • Distribute materials

  • Proficiency testing

  • Proceed with study



Conclusions107 l.jpg
Conclusions competition ELISA)

  • Established that cockroach allergen vaccines need to be standardized

  • Need to establish the potency of candidate US reference materials by bioassay (ID50EAL)

  • Endotoxin issue to be studied in depth


Will overall allergenicity measurements be sensitive to changes in specific allergen levels l.jpg
Will overall allergenicity measurements be sensitive to changes in specific allergen levels?

  • In mite stability study (1998-1999), RP was stable at -20°C and 4°C for up to 12 months

  • Degradation of specific allergens (group 1 and 2; specific bands) was observed at 4°C

Soldatova LN, Paupore EJ, Burk SH, Pastor RW, Slater JE. J Allergy Clin Immunol 2000; 105:482-8.


Rid with monospecific antiserum l.jpg
RID with monospecific antiserum changes in specific allergen levels?

  • Examples: cat, ragweed

  • Advantages

    • quantitative

    • monospecific

  • Disadvantages

    • need to identify relevant allergen(s)


Competition elisa with pooled allergic human sera l.jpg
Competition ELISA with pooled allergic human sera changes in specific allergen levels?

  • Examples: mites, grasses

  • Advantages

    • quantitative

    • reflects spectrum of allergen recognition

    • does not require identification of relevant allergens

  • Disadvantages

    • use of pooled sera

    • effects of fluctuations in individual allergens difficult to measure


Specific loss of a single allergen l.jpg
Specific loss of a single allergen changes in specific allergen levels?


Will overall allergenicity measurements be sensitive to changes in specific allergen levels112 l.jpg
Will overall allergenicity measurements be sensitive to changes in specific allergen levels?

  • Depletion analysis

    • Raise specific antibodies to Bla g 1, 2, 4 and 5

    • Selectively adsorb

    • Test for specific allergen levels

    • Test for overall allergenicity


Sds page of bla g 1 absorbed cockroach antigen l.jpg
SDS-Page of Bla g 1 Absorbed Cockroach Antigen changes in specific allergen levels?

Cr Sham Abs


Selective adsorption of bla g 1 l.jpg

Sham adsorbed changes in specific allergen levels?

Adsorbed with anti-Bla g 1

Bla g 1 ELISA

Selective adsorption of Bla g 1



Conclusions116 l.jpg
Conclusions measured by competition ELISA

  • Established that cockroach allergen vaccines need to be standardized

  • Need to establish the potency of candidate US reference materials by bioassay (ID50EAL)

  • Endotoxin issue to be studied in depth

  • Surrogate test may not be the competition ELISA


Conclusions117 l.jpg
Conclusions measured by competition ELISA

  • Standardized German and American cockroach allergen vaccines will

    • facilitate definitive studies on the role of cockroach allergens in inner city asthma, and on the best methods for eradication and treatment

    • make for safer and more effective products


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