Chemistry and Immunology of Streptococcal M Proteins

University Of Tennessee Health Sci Ctr, Memphis TN

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Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): The overall goal of this project is to systematically collect group A streptococci (GrAS) from throats of North American children with acute streptococcal pharyngitis from diverse geographic primary care locations for characterization of isolates. We have recently completed a phase I clinical trial of a 26-valent group A streptococcal M protein-based vaccine. The efficacy of the vaccine will depend, among other things, on the epidemiology of group A streptococcal infections, including the prevalence of M types in open populations over extended periods of time and the allelic variations that occur in emm genes within a serotype. The specific aims of this supplemental funding request are 1) To determine the distribution of emm types and allelic variation of GrAS isolates from throat cultures of children 3-18 years old from 13 geographic sites in North America with symptomatic acute streptococcal pharyngitis, and to assess the inter-site and the year-to-year variations in emm type distribution, and 2) To use selected clinical isolates to determine the potential protective efficacy of the 26-valent vaccine that is currently in clinical trials. Building upon the surveillance system utilized during the past two respiratory seasons (2000-2001 and 2001-2002), we propose to expand the number of primary care pediatric sites to 13 for the next 3 respiratory seasons, with each site providing a total of 100 GrAS isolates collected from children 3-18 years old during four scheduled periods per season. Specimens (cultures and swabs) will be shipped to Dr. Shulman's Infectious Diseases Laboratory in Chicago, isolated and confirmed as GrAS. DNA will be extracted from overnight growths, stored, catalogued, frozen and then shipped to the Streptococcal Molecular Epidemiology Laboratory of the Centers for Disease Control and Prevention (CDC) for emm gene sequencing, including determination of alleles based upon 650-750 base partial sequences. Frequencies of individual emm types nationally and at each site will be calculated, with inter-site and inter-seasonal assessments made. In addition, all strains will also be assessed for macrolide, clindamycin, and ketolide resistance by microbroth tube dilution studies in the Infectious Diseases Laboratory in Chicago, and correlations will be made between emm type and [unreadable] macrolide resistance. [unreadable] [unreadable]