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

3. Development of a GAS Vaccine F Target identification F Preclinical –Immunogenicity –Animal protection and/or colonization status F Toxicology –Standard toxicology –Tissue cross-reactivity –Histopathology (related to route) F Human clinical trials –Novel vector –Parenteral vs mucosal routes –Dose – concentration and schedule

4. Obstacles in the Development of a GAS Vaccine F Cross-reactivity of M protein epitopes with human tissue (heart, kidney) F Limited animal models –Mouse for skin infections –Macques for pharyngitis (recent) F Immunological studies F Pathogenesis not understood

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

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

7. DMID Partnership Program F 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 F FY03 Initiatives –Biodefense u Vaccines, adjuvants, therapeutics, diagnostics u Clinical resources –Non-biodefense RFA: 03-003 u Novel therapies against hepatitis B virus u 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 F Vaccines –Group A streptococci (GAS) –Group B streptococci (GBS) –Helicobacter pylori F Point of care diagnostics –GAS and GBS

11. Workshop on Prevention of GAS Diseases and their Sequelae F Clinical investigators F Research scientists F Members of international community F US government agencies (NIH, CDC and FDA) F Industrial partners

12. Workshop on Prevention of GAS Diseases and their Sequelae F Identify gaps in scientific understanding F Identify logistical and scientific barriers to evaluation of vaccines F Develop a strategic plan