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Overview of Laboratory of Overview of Laboratory of Bacterial PolysaccharidesBacterial Polysaccharides
Willie F. Vann, Ph.D.Willie F. Vann, Ph.D.
Chief, Laboratory of Bacterial Chief, Laboratory of Bacterial PolysaccharidesPolysaccharides
Description of the Laboratory of Description of the Laboratory of Bacterial PolysaccharidesBacterial Polysaccharides
The Laboratory of Bacterial Polysaccharides The Laboratory of Bacterial Polysaccharides investigates the biochemistry, biology, chemistry, and investigates the biochemistry, biology, chemistry, and immunology ofimmunology of virulence factors of encapsulated virulence factors of encapsulated bacteriabacteria. .
These virulence factors include capsular These virulence factors include capsular polysaccharides, lipopolysaccharides, and outer polysaccharides, lipopolysaccharides, and outer membrane proteins. membrane proteins.
These basic research fields are related to the These basic research fields are related to the regulatory activities of the Laboratory of Bacterial regulatory activities of the Laboratory of Bacterial Polysaccharides which include, review and approval of Polysaccharides which include, review and approval of BLA and IND submissions related to polysaccharide BLA and IND submissions related to polysaccharide and polysaccharide conjugate vaccines in addition to and polysaccharide conjugate vaccines in addition to non-capsular immunogens of encapsulated non-capsular immunogens of encapsulated pathogens.pathogens.
Product ResponsibilitiesProduct Responsibilities Licensed Polysaccharide VaccineLicensed Polysaccharide Vaccine
23 Valent pneumococcal polysaccharide23 Valent pneumococcal polysaccharide Quadravalent meningococcal polysaccharideQuadravalent meningococcal polysaccharide Vi polysaccharideVi polysaccharide
Licensed Glycoconjugate VaccinesLicensed Glycoconjugate Vaccines Quadravalent meningococal-diphtheria toxoidQuadravalent meningococal-diphtheria toxoid Quadravalent meningococcal- CRM197Quadravalent meningococcal- CRM197 13 valent pneumococcal-CRM19713 valent pneumococcal-CRM197 Haemophilus type b –tetanus toxoid (2)Haemophilus type b –tetanus toxoid (2) Haemophilus type b – outer membrane proteinHaemophilus type b – outer membrane protein
(BLA supplements, Inspections, Lot release)(BLA supplements, Inspections, Lot release)
Major Regulatory Accomplishments
Vaccine Date Submitted Date Licensed
Manufacturer
Meningococcal tetravalent ACYW-135 CRM197 Conjugate
8/28/2008 2/19/2010 Novartis
H. influenzae b Tetanus Toxoid Conjugate
3/17/2009 8/19/2009 GSK
Pneumococcal 13-valent CRM197 Conjugate
3/6/2009 2/24/2010 Wyeth
Current Organization of Laboratory ofBacterial Polysaccharides
Laboratory of Bacteria lPolysaccharides
W illie F. Vann, Chief
GlycobiologyWillie F. Vann, PI
Structural BiologyDaron Freedberg, PI
Cellular ImmunologyM ustafa Akkoyunlu,
PI
MolecularEpidemiology
M argaret Bash, PI
Biochemistry ConjugationChemistry
Vaccine StructureJohn Cipollo, PI
BacterialPathogenesisWei Wang, PI
Mustafa Akkoyunlu, PI Mustafa Akkoyunlu, PI - - Cellular Immunology Group Cellular Immunology Group Immunobiology of the host response to capsular Immunobiology of the host response to capsular
polysaccharides of encapsulated bacteria polysaccharides of encapsulated bacteria John Cipollo, PI - Vaccine Structure Group John Cipollo, PI - Vaccine Structure Group
Mass spectrometry (MS) based strategies to investigate Mass spectrometry (MS) based strategies to investigate the role and significance of glycoconjugates in infective the role and significance of glycoconjugates in infective processes processes
Daron Freedberg, PI - Structural Biology Group Daron Freedberg, PI - Structural Biology Group Conformational structure of polysaccharide antigens Conformational structure of polysaccharide antigens
Margaret Bash, PI - Molecular Epidemiology GroupMargaret Bash, PI - Molecular Epidemiology Group Outer membrane protein diversification as it relates to Outer membrane protein diversification as it relates to
vaccine safety and efficacyvaccine safety and efficacy
Major Areas of ResearchMajor Areas of Research
Wei Wang, PI - Bacterial Pathogenesis Wei Wang, PI - Bacterial Pathogenesis Group Group Dr. Wang brings a new expertise to the Dr. Wang brings a new expertise to the
laboratory that is especially relevant to laboratory that is especially relevant to evaluation of vaccines based on genomics. evaluation of vaccines based on genomics.
Genetics of Genetics of M. catarrhalisM. catarrhalis pathogenesis. pathogenesis. Willie F. Vann, PI -Willie F. Vann, PI - Glycobiology Group Glycobiology Group
BiochemistryBiochemistry – Capsular polysaccharide – Capsular polysaccharide biosynthesis; Targeted design of conjugate biosynthesis; Targeted design of conjugate vaccines.vaccines.
Conjugation ChemistryConjugation Chemistry – Methodology for – Methodology for preparation of conjugate vaccines. preparation of conjugate vaccines.
Some Highlights of Research Effort Some Highlights of Research Effort in the Laboratory of Bacterial in the Laboratory of Bacterial
PolysaccharidesPolysaccharides
CIPOLLO: CIPOLLO: Caenorhabditis elegans Caenorhabditis elegans as a Surrogate Model as a Surrogate Model for Glycan Dependent Host Infectionfor Glycan Dependent Host Infection
Over 40 microbes infect C. elegans: most of which are human pathogens or their close relatives. Infectious agents requiring host glycoconjugates to infect C. elegans :
Yersinia pestis and Y. pseudotuberculosis Bacillus thuringiensis: crystal toxin (Cry5B) binds to glycolipid leading to
lethal infection. ‘bre’ gene family Coprinopsis cinerea: fungal pathogen galectin CGL2 binds to the N-glycan
core Staphylococcus aureus Microbacterium nematophilum
Glycans
Permethylation
MALDI-MS
999.0 1799.4 2599.8 3400.2 4200.6 5001.0
Mass (m/z)
0
1.3E+4
0
10
20
30
40
50
60
70
80
90
100
% In
tens
ity
Voyager Spec #1[BP = 1579.0, 12902]
FREEDBERG: Determination of Structural Epitopes in Polysaccharides using High Field NMR Techniques
Intraresidue H-bond
2.5Å
WANG: Pathogenic Role of a WANG: Pathogenic Role of a Moraxella catarrhalis Moraxella catarrhalis Denitrification PathwayDenitrification Pathway
HBE only O35E wt O35E narGH O35E aniA O35E norB
AniA NorB
NO N2ONO2-NO3
-NarGHJI
Relevance of Research Program to Relevance of Research Program to CBER MissionCBER Mission
The Laboratory of Bacterial Polysaccharides has The Laboratory of Bacterial Polysaccharides has regulatory responsibility for vaccines against regulatory responsibility for vaccines against encapsulated bacteria and products containing bacterial encapsulated bacteria and products containing bacterial polysaccharides. polysaccharides.
The overall goal of the research program of the The overall goal of the research program of the Laboratory of Bacterial Polysaccharides is to understand Laboratory of Bacterial Polysaccharides is to understand the virulence factors that are components of vaccines the virulence factors that are components of vaccines against bacterial pathogens. against bacterial pathogens.
The research program of the Laboratory of Bacterial The research program of the Laboratory of Bacterial Polysaccharides is directed toward understanding the Polysaccharides is directed toward understanding the physical, chemical, and immunological properties of physical, chemical, and immunological properties of bacterial polysaccharides, and vaccines against bacterial polysaccharides, and vaccines against encapsulated bacteria.encapsulated bacteria.
The knowledge and expertise gained The knowledge and expertise gained in this research endeavor provide a in this research endeavor provide a scientific basis for our decisions scientific basis for our decisions related to the review of related to the review of manufacturing, purity, potency, and manufacturing, purity, potency, and safety of carbohydrate containing safety of carbohydrate containing vaccines. vaccines.