Overview of the Laboratory of

Respiratory and Special Pathogens

Michael Schmitt, Ph.D.Chief, Laboratory of Respiratory

and Special Pathogens

Overview of LRSP

Principal Investigators in LRSP – Research/Reviewers:

-To develop and direct a research program -Participate in the regulatory activities of LRSP.

The research is broad in scope--and varies from basic studies that address questions on bacterial virulence --to studies that provide insight into the functional characteristics of current and future vaccines

The research is supportive of the regulatory activities of the

laboratory…Product review for a diverse group of bacterial

vaccines

Regulatory ResponsibilitiesRegulatory Responsibilities

Primary Licensed Vaccines (combinations)Diphtheria vaccinesTetanus vaccinesPertussis vaccines

Bio-defense VaccinesAnthrax vaccines (licensed)Plague vaccinesBotulinum vaccinesRicin Vaccines

Other VaccinesStaphylococcus aureus vaccinesStreptococcal vaccinesClostridial vaccines

Regulatory activitiesRegulatory activities

Pre-approval Review of IND and IND amendmentsReview of IND and IND amendments Review of BLAsReview of BLAs

Post-approvalPost-approval BLA supplements (product or BLA supplements (product or

clinical)clinical) Lot releaseLot release InspectionsInspections

Current Organization of LRSP

LRSP Staff

Regulatory Activities of LRSP

Regulatory Regulatory

Burns Research ProgramBurns Research Program

•Anthrax vaccines Analysis of the antibody response

to anthrax vaccines Improving anthrax vaccine

stability

• Staphylococcus aureus vaccines Identification of potential vaccine

antigens Elucidation of correlates of

immunity

Burns Research Program

• Facilitates optimization of manufacturing Facilitates optimization of manufacturing methods for anthrax vaccinesmethods for anthrax vaccines

• Provides information used in the Provides information used in the development of quality control tests for development of quality control tests for anthrax and anthrax and S. aureusS. aureus vaccines vaccines

• Supplies important information for Supplies important information for assessing efficacy of new anthrax and assessing efficacy of new anthrax and S. S. aureusaureus vaccines vaccines

Keller Research ProgramKeller Research Program

•Botulinum and Tetanus Botulinum and Tetanus Toxoid VaccinesToxoid Vaccines

Improve toxoid testing strategies Improve toxoid testing strategies resulting in improved antigen resulting in improved antigen quality controlquality control

Develop assays to better assess Develop assays to better assess the quality of botulinum and the quality of botulinum and tetanus antibodiestetanus antibodies

Evaluate antitoxin preparations Evaluate antitoxin preparations for use as reference standardsfor use as reference standards

Keller Research ProgramKeller Research Program

• Fosters development of improved botulinum Fosters development of improved botulinum toxoid vaccines and antitoxins to enhance toxoid vaccines and antitoxins to enhance preparedness against bioterror attackspreparedness against bioterror attacks

• Provides the scientific foundation for evaluating Provides the scientific foundation for evaluating botulinum toxoid and tetanus toxoid vaccinesbotulinum toxoid and tetanus toxoid vaccines

Merkel Research Merkel Research ProgramProgram

•Pertussis vaccinesPertussis vaccines Development and use of the baboon model of Development and use of the baboon model of

pertussis to study pertussis pathogenesis and the pertussis to study pertussis pathogenesis and the immune response to infection and vaccination.immune response to infection and vaccination.

Development of aerosol models of pertussis to Development of aerosol models of pertussis to identification and characterize factors contributing identification and characterize factors contributing to transmission of to transmission of B. pertussisB. pertussis

• Anthrax vaccinesAnthrax vaccines Development of cost-effective models of pulmonary Development of cost-effective models of pulmonary

anthrax for screening and early development of anthrax for screening and early development of anthrax vaccines and therapeutic products anthrax vaccines and therapeutic products

Characterization of innate immune recognition of Characterization of innate immune recognition of pulmonary anthraxpulmonary anthrax

• Staphylococcus aureusStaphylococcus aureus vaccines vaccines Development of models of staphylococcal systemic, Development of models of staphylococcal systemic,

implant, and skin infections for evaluating implant, and skin infections for evaluating candidate vaccine antigenscandidate vaccine antigens

Merkel Research Merkel Research ProgramProgram

• Provides important insights into vaccine-mediated Provides important insights into vaccine-mediated protection against pertussis leading to enhanced protection against pertussis leading to enhanced understanding of the resurgence of pertussis in the U.S. understanding of the resurgence of pertussis in the U.S. and potential public health responses to the pertussis and potential public health responses to the pertussis problem.problem.

• Furthers development of new vaccines and post-exposure Furthers development of new vaccines and post-exposure treatments for pertussis, anthrax and treatments for pertussis, anthrax and S. aureus S. aureus infectionsinfections

• Provides resources critical for the early development and Provides resources critical for the early development and evaluation of new bacterial vaccinesevaluation of new bacterial vaccines

• Provides the scientific foundation for evaluation of Provides the scientific foundation for evaluation of pertussis, anthrax, and pertussis, anthrax, and S. aureusS. aureus vaccines vaccines

Schmitt Research Schmitt Research ProgramProgram

•Diphtheria VaccinesDiphtheria Vaccines

Characterization of the Hmu iron transport Characterization of the Hmu iron transport system of system of Corynebacterium diphtheriaeCorynebacterium diphtheriae

Proteins of this system are Proteins of this system are coordinately expressed with coordinately expressed with diphtheria toxin and are therefore diphtheria toxin and are therefore expected to be produced during expected to be produced during infectioninfection

Cell surface components of this Cell surface components of this system share similarity with system share similarity with virulence in other disease-causing virulence in other disease-causing gram positive bacteriagram positive bacteria

Analysis of heme-dependent regulatory Analysis of heme-dependent regulatory systems of systems of C. diphtheriaeC. diphtheriae

Schmitt Research Program

• Provides a better understanding of pathogenic mechanisms of Provides a better understanding of pathogenic mechanisms of C. C. diphtheriaediphtheriae facilitating development of new or improved facilitating development of new or improved diphtheria vaccinesdiphtheria vaccines

• Provides information about potential new immunogens for gram-Provides information about potential new immunogens for gram-positive bacterial vaccinespositive bacterial vaccines

• Provides the scientific foundation for evaluation of new vaccines Provides the scientific foundation for evaluation of new vaccines containing diphtheria components as well as review of the containing diphtheria components as well as review of the numerous ongoing changes and adjustments required to numerous ongoing changes and adjustments required to maintain and improve the quality of licensed diphtheria toxoid-maintain and improve the quality of licensed diphtheria toxoid-containing vaccinescontaining vaccines

Of note, approximately 25% of all licensed vaccines distributed Of note, approximately 25% of all licensed vaccines distributed in the U.S contain a diphtheria toxoid component.in the U.S contain a diphtheria toxoid component.

Relevance of Research to Relevance of Research to RegulationRegulation

Knowledge acquired from our research Knowledge acquired from our research establishes a scientific basis for our decisions in establishes a scientific basis for our decisions in the regulations of vaccines.the regulations of vaccines.

Provides a in-depth understanding of novel productsProvides a in-depth understanding of novel products

Expertise to best design the tests to assess the safety, Expertise to best design the tests to assess the safety, purity and potency of vaccinespurity and potency of vaccines

Expertise to design the efficacy studies for vaccines Expertise to design the efficacy studies for vaccines licensed under the Animal Rulelicensed under the Animal Rule

Credibility in the scientific community. Provides Credibility in the scientific community. Provides assurances that we possess the scientific qualifications assurances that we possess the scientific qualifications to assess safety and quality of current and the next to assess safety and quality of current and the next generation of vaccinesgeneration of vaccines