GM1 BINDING DEFICIENT EXOTOXINS FOR USE AS IMMUNOADJUVANTS

摘要

Addition of a bacterial ADP-ribosylating exotoxin (bARE) to a formulation (e.g., immunogen or vaccine) or a system (e.g., patch or kit) for immunization enhances the immune response in a subject to one or more components of the formulation. Binding of the B subunit of a BARE to ganglioside GM1 of the subject in vivo, however, mediates toxicity and limits the use of native bARE as adjuvants. Mutation or in vitro coupling of the B subunit to ligands such as GMl inhibits binding to GM1 in vivo, thereby eliminating toxicity but retaining desired adjuvant activity. The use of such detoxified, GM-1 binding deficient exotoxins provides a safe and potent new strategy for development of effective formulation for immunization.