. "Appendix D-16: The Prospects for Immunizing Against Streptococcus Group A." New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press, 1986.
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New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
Streptococci are spherical or ovoid bacteria that grow in pairs or chains of varying lengths. They are gram-positive, non-spore-forming, catalase-negative, and ordinarily nonmotile. They have complex and variable nutritional requirements.
Taxonomically, these organisms belong to the family Sreptococcaceae, genus Streptococcus, of which there are 21 identified species. When streptococci are cultivated on blood agar plates, they may produce complete (beta) hemolysis, partial (alpha) hemolysis, or no (gamma) hemolysis. More precise differentiation of streptococci can be made by immunologic means. The organisms may be separated into serogroups by means of antigenic differences in the cell wall carbohydrates or teichoic acids. The group A streptococcus, also known as Streptococcus pyogenes, is facultatively anaerobic, beta-hemolytic (with very rare exceptions), and contains in its cell wall a group-specific carbohydrate composed of rhamnose and N-acetyl-glucosamine. There are a number of other important substances expressed on the streptococcal surface. These include lipoteichoic acid, the principal ligand responsible for adherence of GrAS to epithelial surfaces, and a variety of proteins designated as M, T, and R. Of these, by far the most important is M protein.
M protein is the major virulence antigen of GrAS. Strains rich in this protein are resistant to phagocytosis by polymorphonuclear leukocytes, multiply rapidly in fresh human blood, and are capable of initiating disease. Strains lacking M protein are avirulent. Group A streptococci may be divided into serotypes on the basis of antigenic differences in M protein molecules. Over 70 such serotypes are currently recognized. Human immunity to streptococcal infection is based on the development of type-specific opsonic antibodies directed against the anti-phagocytic moiety of M protein. In rare instances, cross-protection by antibody to one type against organisms of a heterologous type has been demonstrated.
The M protein molecule penetrates the cell wall; this configuration localizes the type-specific antigen on the tips of hair-like fimbrillae protruding from the cell surface. The manner in which M protein exerts its anti-phagocytic effect is under investigation. The protein prevents interaction of the streptococcal cell wall with complement components, an effect that is enhanced by the ability of M protein to precipitate fibrinogen directly onto the bacterial surface. This protective effect is nullified by the presence of adequate concentrations of type-specific antibody.
T protein serves as the basis for a subsidiary typing system for GrAS. Another important somatic component of the streptococcus is the hyaluronic acid capsule. This capsule is also anti-phagocytic and serves as an auxiliary virulence factor.
For many years, it has been recognized that the ability to initiate AGN is limited to strains of certain GrAS serotypes (e.g., types 1, 4, 12, 49, 55, and a few others). Although this distinction between nephritogenic and nonnephritogenic GrAS is well established, there has been considerably more controversy over the issue of whether GrAS vary