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 f...

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Bibliographic Details
Published in:The Journal of infectious diseases 1996-08, Vol.174 (2), p.338-345
Main Authors: Bavari, Sina, Dyas, Beverly, Ulrich, Robert G.
Format: Article
Language:English
Subjects:
Animal bacterial diseases
Animals
Antibodies
Bacterial diseases
Biological and medical sciences
Enterotoxins
Enterotoxins - genetics
Enterotoxins - immunology
Enterotoxins - therapeutic use
Genes, MHC Class II
Histocompatibility Antigens Class II
Infectious diseases
Major Articles
Male
Medical sciences
Mice
Mice, Inbred C57BL
Molecules
Mutation
Receptors, Antigen, T-Cell
Staphylococcal Infections - prevention & control
Staphylococcal Vaccines - therapeutic use
Staphylococcus
Superantigens
Superantigens - genetics
Superantigens - immunology
Superantigens - therapeutic use
T cell antigen receptors
T lymphocytes
Toxicity
Toxins
Vaccination
Vaccines, Attenuated - therapeutic use
Vaccines, Synthetic - therapeutic use
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Summary: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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/174.2.338