Update on the Development of a Group A Streptococcal Vaccine

1
Update on the Development of a Group A
Streptococcal Vaccine

• Fran A. Rubin, Ph.D.
• Program Officer for Group A Streptococci
• Respiratory Diseases Branch
• Division of Microbiology and Infectious Diseases
• National Institute of Allergy and Infectious
  Diseases
• National Institutes of Health
• Department of Health and Human Services

2
NIAID Activities

• Basic Research
• Genomic sequencing (M1, M3 and M18)
• Contracts for applied clinical research
• Partnerships with industry
• Clinical trial network
• Workshop (NVPO support)

3
Development of a GAS Vaccine

• Target identification
• Preclinical
• Immunogenicity
• Animal protection and/or colonization status
• Toxicology
• Standard toxicology
• Tissue cross-reactivity
• Histopathology (related to route)
• Human clinical trials
• Novel vector
• Parenteral vs mucosal routes
• Dose concentration and schedule

4
Obstacles in the Development of a GAS Vaccine

• Cross-reactivity of M protein epitopes with human
  tissue (heart, kidney)
• Limited animal models
• Mouse for skin infections
• Macques for pharyngitis (recent)
• Immunological studies
• Pathogenesis not understood

5
Recent advances/opportunities

• Genomic sequencing/proteomics/microarrays
• Identification of new targets
• Immunogenetic studies
• Specific leukocyte antigen class II haplotypes
  associated with protection/risk of severe disease
• Epidemiology studies
• Current data on circulating M serotypes
• Longitudinal surveillance in school children

6
Vaccine Candidates

• M protein based
• Type-specific-Jim Dale
• Conserved region-Vince Fischetti
• Combination-Michael Good
• Surface proteins
• C5a peptidase - Pat Cleary
• Sfb Singh Chhatwal
• Streptococcal pyrogenic exotoxins
• Spe A and/or C Pat Schlievert
• Spe B Jim Musser

7
DMID Partnership Program

• Industry participation
• To facilitate collaborative partnerships among
  industry, academia, and government to develop
  novel approaches for controlling infectious
  diseases.

8
Partnerships for Product Development

• Target identification
• Preclinical development
• Clinical trials

9
DMID Partnership Program

• FY03 Initiatives
• Biodefense
• Vaccines, adjuvants, therapeutics, diagnostics
• Clinical resources
• Non-biodefense RFA 03-003
• Novel therapies against hepatitis B virus
• Strategies for control of arthropod vector-borne
  diseases

• http//grants1.nih.gov/grants/guide/rfa-files/RFA-
  AI-03-003.html

10
Partnership FY04 Initiative

• Vaccines
• Group A streptococci (GAS)
• Group B streptococci (GBS)
• Helicobacter pylori
• Point of care diagnostics
• GAS and GBS

11
Workshop on Prevention of GAS Diseases and their
Sequelae

• Clinical investigators
• Research scientists
• Members of international community
• US government agencies
• (NIH, CDC and FDA)
• Industrial partners

12
Workshop on Prevention of GAS Diseases and their
Sequelae

• Identify gaps in scientific understanding
• Identify logistical and scientific barriers to
  evaluation of vaccines
• Develop a strategic plan