overview of laboratory of bacterial polysaccharides by willie f. vann, chief lbp
TRANSCRIPT
Overview of Laboratory Overview of Laboratory of Bacterial of Bacterial
PolysaccharidesPolysaccharides
ByBy
Willie F. Vann, Chief LBPWillie F. Vann, Chief LBP
Description of the Laboratory of Bacterial Description of the Laboratory of Bacterial PolysaccharidesPolysaccharides
The Laboratory of Bacterial The Laboratory of Bacterial Polysaccharides investigates the Polysaccharides investigates the biochemistry, biology, chemistry, and biochemistry, biology, chemistry, and immunology of virulence factors of immunology of virulence factors of encapsulated bacteria. encapsulated bacteria.
These virulence factors include capsular These virulence factors include capsular polysaccharides, lipopolysaccharides, polysaccharides, lipopolysaccharides, and outer membrane proteins. and outer membrane proteins.
Description of the Laboratory of Bacterial Description of the Laboratory of Bacterial Polysaccharides (continued)Polysaccharides (continued)
The Laboratory of Bacterial The Laboratory of Bacterial Polysaccharides has review Polysaccharides has review responsibility for submissions related responsibility for submissions related to polysaccharide and polysaccharide to polysaccharide and polysaccharide conjugate vaccines in addition to conjugate vaccines in addition to non-capsular immunogens of non-capsular immunogens of encapsulated pathogens.encapsulated pathogens.
Chronology of Laboratory of Bacterial Chronology of Laboratory of Bacterial PolysaccharidesPolysaccharides
20022002– Last Site VisitLast Site Visit
20042004– CE Frasch steps down as Lab ChiefCE Frasch steps down as Lab Chief– MS Blake becomes Acting Lab ChiefMS Blake becomes Acting Lab Chief
20062006– WF Vann appointed Lab ChiefWF Vann appointed Lab Chief– Glycobiology Group of Lab of Bacterial Toxins Glycobiology Group of Lab of Bacterial Toxins
joined Lab of Bacterial Polysaccharidesjoined Lab of Bacterial Polysaccharides– NMR and Mass Spectrometry groups of Lab of NMR and Mass Spectrometry groups of Lab of
Biophysics joined Lab of Bacterial Biophysics joined Lab of Bacterial PolysaccharidesPolysaccharides
Current Organization of the Laboratory Current Organization of the Laboratory of Bacterial Polysaccharidesof Bacterial Polysaccharides
Labo rato ry o f Bacte r ialPo lysacch arid e s
W illie F. V ann , Ch ief
Glyco b io logyW illie F. V ann ,PI
Structu ral Bio log yDaron Freedb erg,
PI
An alyticalBio che mistry
ChaoMing Tsai, PI
Path og e ne sisMilan S. Blake, PI
Ce llu lar Immuno lo gyMu stafa Akkoyun lu ,
PI
Molecu larEpidemiology
Bioch emistry Con jugationChemistry
Vaccine Structu reJoh n Cip o llo , PI
Hug o Azurm e ndiPos tdoctoral Fe llow
Sco tt Norr isNM R S pe ctrom e trist
Structural Bio lo gyDaron Freedb erg, PI
F lora LichaaChe mist
The re sa W a ngBiologist
An alyticalBio che mistry
ChaoMing Tsai, PI
Su n ita Kansw alPos tdoctoral Fe llow
Nora Katse n e lsonBiologist
Ce llu lar Immun o logyM ustafa A k k oyunlu, PI
CURRENT RESEARCH STAFF
Glycobiology Group
Willie F. Vann, PI
Conjugate ChemistryRobert Lee, PhD, SS
Amy KuoBritany Bowen
BiochemistryEkaterina Andreishcheva
Seshu GudlavalettiJustine VionnetDwight Peterson
Molecular Epidemiology
Margaret Bash, MD, MOIvano Felippis
Craig Hammack
Vaccine StructureJohn Cipollo, PI(April, 2007)
Mass Spectrometrist(new recruit)
Postdoctoral Fellow(new recruit)
Areas of ResearchAreas of Research
Structure and conformation of capsular Structure and conformation of capsular polysaccharidespolysaccharides
Biosynthesis of capsular polysaccharidesBiosynthesis of capsular polysaccharides Role of non-capsular antigens in Role of non-capsular antigens in
protectionprotection Interaction of the capsular Interaction of the capsular
polysaccharides with the immune systempolysaccharides with the immune system Development of methodology for Development of methodology for
analysis of conjugate vaccinesanalysis of conjugate vaccines
Relevance of Research Program to Relevance of Research Program to CBER MissionCBER Mission
The Laboratory of Bacterial The Laboratory of Bacterial Polysaccharides has regulatory Polysaccharides has regulatory responsibility for vaccines against responsibility for vaccines against encapsulated bacteria and products encapsulated bacteria and products containing bacterial polysaccharides containing bacterial polysaccharides
The overall goal of the research program The overall goal of the research program of the LBP is to understand the virulence of the LBP is to understand the virulence factors that are components of vaccines factors that are components of vaccines against bacterial pathogens. against bacterial pathogens.
Relevance of Research Program to Relevance of Research Program to CBER Mission (continued)CBER Mission (continued)
The research program of the Laboratory of The research program of the Laboratory of Bacterial Polysaccharides is directed Bacterial Polysaccharides is directed toward understanding the physical, toward understanding the physical, chemical, and immunological properties of chemical, and immunological properties of bacterial polysaccharides, and bacterial polysaccharides, and polysaccharide conjugate vaccines polysaccharide conjugate vaccines
The knowledge and expertise gained in The knowledge and expertise gained in this research endeavor provide a scientific this research endeavor provide a scientific basis for our decisions related to the basis for our decisions related to the review of manufacturing, purity, potency, review of manufacturing, purity, potency, and safety of carbohydrate containing and safety of carbohydrate containing vaccines. vaccines.
Some Significant AchievementsSome Significant Achievements Development of Efficient Method for Development of Efficient Method for
Meningococcal Group A Conjugate Meningococcal Group A Conjugate Vaccine SynthesisVaccine Synthesis– Vaccine in MVP/WHO Sponsored Phase II Vaccine in MVP/WHO Sponsored Phase II
Clinical TrialClinical Trial
Meningococcal Group A Conjugate Vaccine ProjectMeningococcal Group A Conjugate Vaccine Projectmanaged by CE Frasch - CBER & M. LaForce – MVP managed by CE Frasch - CBER & M. LaForce – MVP
SerologyCDC
Margaret Bash
Conjugate TechnologyRobert Lee/DBPAP
Manufacturing Serum Institute of India
FundingPATH /MVP
Men A VaccineProject
Daron Freedberg and Scott Norris contributed to analysis during development
Gates Foundation
Some Significant AchievementsSome Significant AchievementsAnalytical Biochemistry – ChaoMing Tsai, PIAnalytical Biochemistry – ChaoMing Tsai, PI
Developed HPAEC method for quantitation Developed HPAEC method for quantitation of phosphate and acetylation in of phosphate and acetylation in polysaccharide vaccinespolysaccharide vaccines
Characterized the Characterized the lgtlgtH gene of H gene of NeisseriaNeisseria LOS gene clusterLOS gene cluster
Demonstrated that the LOS of commensal Demonstrated that the LOS of commensal N. polysacchareaN. polysaccharea is similar to LOS of is similar to LOS of meningococcal pathogenmeningococcal pathogen
Some Significant AchievementsSome Significant AchievementsMolecular Epidemiology – Margaret BashMolecular Epidemiology – Margaret Bash
Developed and applied molecular Developed and applied molecular methods to study PorB diversitymethods to study PorB diversity
Horizontal genetic exchange (mosaicism) Horizontal genetic exchange (mosaicism) predominatespredominates
Persistence of PorB variable region sequence Persistence of PorB variable region sequence types indicates diversification is constrainedtypes indicates diversification is constrained
Identified survival advantages associated Identified survival advantages associated with PorB typeswith PorB types
Relevant to development and evaluation of Relevant to development and evaluation of broadly protective OMP vaccines broadly protective OMP vaccines
Some Significant AchievementsSome Significant AchievementsCellular Immunology-Mustafa Akkoyunlu, PICellular Immunology-Mustafa Akkoyunlu, PI
Interactions of bacterial capsular polysaccharides with innate immune system.
– Neisseria meningitidis type C polysaccharide binding to CD14 and LBP inhibits meningococcal LPS mediated cell activation
Modulation of BAFF/APRIL system molecules by microbial products.
– Decreased expression of TACI on newborn mouse B cells may to be responsible for the impaired response of newborns to polysaccharide antigens.
– Toll-like receptor agonists, CpG DNA and LPS, strongly upregulate TACI expression on B cells.
Some Significant AchievementsSome Significant Achievements Structural Biology-Daron Freedberg, PIStructural Biology-Daron Freedberg, PI
1. 1. On cell NMR: On cell NMR: In-vivoIn-vivo antigen characterization by NMR antigen characterization by NMRMening B PSMening B PS structure structure on cellson cells = = Mening B PSMening B PS structure in vaccine structure in vaccine
2. Carbohydrate 3D Structure: Sucrose
m=monomer
p=polymer
HOO
H
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Licensed Product ResponsibilityLicensed Product ResponsibilityVaccine ClassVaccine Class ProductProduct ManufacturerManufacturer
PolysaccharidePolysaccharide Pneumococcal 23-valentPneumococcal 23-valent WyethWyeth
MerckMerck
Meningococcal tetravalentMeningococcal tetravalent Sanofi PasteurSanofi Pasteur
Typhoid ViTyphoid Vi Sanofi PasteurSanofi Pasteur
ConjugateConjugate Haemophilus influenzaeHaemophilus influenzae type b type b WyethWyeth
Sanofi PasteurSanofi Pasteur
Merck (2)Merck (2)
Pneumococcal heptavalentPneumococcal heptavalent WyethWyeth
Meningococcal tetravalentMeningococcal tetravalent Sanofi PasteurSanofi Pasteur
Regulatory ResponsibilitiesRegulatory Responsibilities
Lot ReleaseC-M Tsai
(Formerly CJ Lee)
Theresa Wang Performs Lot Release Tests on Fraction of Submitted Samples
Approximate 400 Samples and Protocols Submitted
Per Year
Regulatory AccomplishmentsRegulatory Accomplishments
Licensing Tetravalent Meningococcal Licensing Tetravalent Meningococcal Conjugate Diphtheria Toxoid Vaccine Conjugate Diphtheria Toxoid Vaccine – against groups A,C, Y, and W-135– against groups A,C, Y, and W-135– Reviewers included Frasch, Tsai, Lee, Reviewers included Frasch, Tsai, Lee,
Bash, Lynn, BlakeBash, Lynn, Blake Significant Changes in Analytical Significant Changes in Analytical
Methodology for Lot ReleaseMethodology for Lot Release– Reviewers included Tsai, FreedbergReviewers included Tsai, Freedberg
Other Regulatory AccomplishmentsOther Regulatory Accomplishments
IND Supplement Reviewed – 350IND Supplement Reviewed – 350 BLA & BLA Supplement Review -85BLA & BLA Supplement Review -85 Participated in International and Participated in International and
CBER Policy Working GroupsCBER Policy Working Groups Distributed Reference Material for Distributed Reference Material for
Haemophilus and Pneumococcal Haemophilus and Pneumococcal Antibody AssaysAntibody Assays