Overview Laboratory of Bacterial

Polysaccharides

From cover - Science, 23 March, 2001

The Laboratory of Bacterial Polysaccharides

The mission of this Laboratory is unified around the fact that:

Most all invasive bacterial diseases in the youngpediatric population are caused by bacterial specieshaving polysaccharide capsules:

• Haemophilus influenzae

• Neisseria meningitidis

• Streptococcus pneumoniae

• Streptococcus agalactiae (Group B Strep)

Licensed Vaccines for which the LBP has Product Responsibility

Polysaccharides:

• Pneumococcal 23-valent Merck

• Meningococcal 4-valent Aventis Pasteur

• Typhoid Vi Aventis Pasteur

Conjugates: • Haemophilus influenzae type b (Hib) Wyeth

Aventis Pasteur Merck (2 )• Pneumococcal 7-valent Wyeth

Combination vaccines

Current Regulatory Activities in the Laboratory of Bacterial Polysaccharides

O IND supplement review – over 125 active INDs

o Product License application and supplement review

Over 80 submissions since June 2000

o Meetings and conference calls with manufacturers

o Lot release protocol review and lot release testing

Approximately 400 protocols per year

o Assist in training of reviewers and inspectors

o Participate in inspections of manufacturing facilities

o Presentations to VRBPAC

Major outside mission related activities by Laboratory of Bacterial

Polysaccharides Personnel

Temporary consultants to CDC, PAHO, WHO and PATH

Help draft WHO requirements for conjugate vaccines

Review Red Book chapters on polysaccharide

and conjugate vaccines

Journal review – multiple journals

Grant review for Meningitis Research Foundation

Review of Military Infectious Disease Research Program

On organizing committees for major workshops

Consult/train foreign laboratories in Quality Control

Research in the Laboratory of Bacterial Polysaccharides

The LBP is responsible for: Conducting basic and applied research

on problems related to the preparation, purity, stability, and immunogenicity of investigational and licensed vaccines for encapsulated bacterial pathogens.

Evaluating host-parasite interactions for pathogenesis and protective immunity.

Organization of the Laboratory of Bacterial Polysaccharides

Carl E. Frasch, Ph.DLaboratory Chief

Pathogenic NeisseriaSection

Margaret C Bash, MDMedical Officer

LipopolysaccharideSection

Chao-Ming Tsai, Ph.D.Biochemist

Polysaccharide and ConjugateVaccine QC Lot Release

Chi-Jen Lee, Sc.D.Biochemist

Polysaccharide ImmunitySection

Carl E. Frasch, Ph.DMicrobiologist

Cellular ImmunologySection

Mustafa Akkoyunlu, MD, Ph.D.Immunologist

Research Objectives: Polysaccharide Immunity Section

Conducts research to evaluate the ability of polysaccharide and conjugate vaccines to induce protective immunity.

Studies different conjugation chemistries to improve conjugate yields and to improve the immune response to native polysaccharide epitopes

Research Objectives: Cellular Immunity Section

Focuses on the initial phase of polysaccharide vaccine/encapsulated bacteria interaction with host immunity.

Seeks to define the interaction of polysaccharides with toll-like receptors (TLRs) on innate cells. The biological events resulting from this interaction may affect the development of adaptive immune responses against polysaccharides.

Investigates the role of “A proliferation-inducing ligand” (APRIL) and B Lymphocyte Stimulator (BLyS) in infant and adult immune responses against bacterial polysaccharides.

Research Objectives: Pathogenic Neisseria Section

Investigates the Por B proteins of Neisseria gonorrhoeae and Neisseria meningitidis.

Studies the natural epidemiology of Por variation

using novel molecular typing methods

  Evaluates the effects of Por variation on host-pathogen

interaction including immune responses to Por, structure

function restrictions on Por, and transmission patterns

Identifies the mechanisms of Por variation through

investigation of mixed infections, diverse and clonal

populations.

 

Research Objectives: Lipopolysaccharide Section

Conducts research to evaluate chemically or genetically detoxified meningococcal LPS bound to protein as a potential vaccine for group B meningococcal disease.

Studies the genetics of LPS biosynthesis in pathogenic and commensal Neisseria species and characterizes their LPS immunochemically.

Thank you