In this proposal the investigator plans to study the immunogenicity of the Group A carbohydrate of Streptococcus pyogenes . The hypothesis upon which this proposal is based is that the broad based immunity to Streptococcus pyogenes infection seen in adults is due to antibodies generate to the group A carbohydrate and that this antigen could be developed into an effective human vaccine. To resolve this hypothesis, the investigator proposes the following five specific aims. 1) To study the immunogenicity of the carbohydrate using different adjutants compatible with administration to humans, 2) To prove that passively administered antibodies to the group A carbohydrate will protect against infection with different Streptococcus pyogenes strains, 3) To prove that active immunization with the group A carbohydrate will give broad protection, 4) To define the relationship between protection against Streptococcus pyogenes and the level of anti A carbohydrate antibodies in patients sera and 5) to investigate the possibility that group A carbohydrate antibodies may react with mammalian tissues. As per Scientific Abstract; Basically this is a three-year proposal to examine the potential role of the group A streptococcal cell wall carbohydrate in evoking opsonic and protective antibodies in mice and humans, which could then be used to protect against a variety of M type strains.
The specific aims are: 1. To develop immunization procedures to achieve high tittered anti-group A carbohydrate antibodies in rabbits and mice for use in opsonic and protective studies. 2. To define the protective activity of the rabbit anti-A CHO antibodies in mice against a variety of group A streptococcal M types. 3. To actively immunize mice with A CHO vaccines and determine the protective efficacy of actively produced antibody against various group A streptococcal M types. 4. To examine the concentration of A CHO antibodies by ELISA in patients with streptococcal related diseases such as ARF and APSGN at the onset and at intervals after disease and in normals of the same age groups. The sera collected will be examined for opsonic and protective activity. 5. The anti-A CHO antibodies from rabbits, mice, and humans will then be examined for cross reactions with mammalian antigens or cytoskeletal proteins by immunofluorescence and ELISA.
