Superantigen vaccines: a comparative study of genetically attenuated receptor-binding mutants of staphylococcal enterotoxin A.
Superantigens exert their pathologic effects by direct binding to major histocompatibility complex (MHC) class II molecules and T cell antigen receptors (TCR), thus circumventing the normal, antigen-specific immune response. A direct link between disease and toxin suggests an excellent opportunity for vaccine intervention. Site-directed mutants of staphylococcal enterotoxin A (SEA) that have attenuated binding to either the TCR or the MHC class II molecule were developed. Both kinds of SEA mutants induced high levels of antibody against SEA when used as vaccines, and the immunized animals were fully protected when challenged with wild type toxin. However, a residual lethality was associated with the attenuated TCR-binding mutant. These results, combined with an understanding of the molecular nature of superantigen and receptor interactions, indicate that targeting MHC class II binding by site-directed mutagenesis will produce the most effective vaccine.
Bavari
S
S
Department of Cell Biology and Biochemistry and of Molecular Biology and Immunology, Army Medical Research Institute of Infectious Diseases, Frederick, Maryland 21702-5011, USA.
Dyas
B
B
Ulrich
R G
RG
D000818:Animals; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011948:Receptors, Antigen, T-Cell; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000627:therapeutic use*; D018089:Superantigens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D013209:Staphylococcal Vaccines; D018089:Superantigens; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C026066:enterotoxin A, Staphylococcal