Adjuvant activities of mutants of LT-IIa and LT-IIb enterotoxin lacking binding to ganglioside
View Patent ↗The present invention describes the adjuvant activity of mutants of LT-IIa and LT-IIb enterotoxin which lack ganglioside binding activity. The adjuvant activity of the LT-IIb(T13I) mutant is comparable to that of the wild type LT-IIb. The adjuvant activity of LT-IIa(T34I) mutant is also described which exhibits a late onset adjuvant activity. These mutants are useful for enhancing immune response to antigens.
1. A method of enhancing immune response to an antigen comprising co-administering intranasally to an individual
(a) a mutant enterotoxin wherein the mutant enterotoxin is a mutant of the B subunit of E. coli LT-IIb and does not exhibit GD1a, GM2 and GM3 ganglioside binding activity as demonstrated by ganglioside-dependent enzyme-linked immunosorbent assay (ELISA), and wherein the mutant enterotoxin consists of the amino acid sequence of SEQ ID NO:6; and
(b) the antigen,
whereby the mutant enterotoxin acts as an adjuvant to enhance the immune response to the antigen, and wherein the immune response comprises a serum antibody response, a salivary antibody response, and a vaginal antibody response to the antigen.
2. The method of claim 1 , wherein the individual is a human.
3. The method of claim 1 , wherein the mutant enterotoxin and the antigen are co-administered as a fused molecule.
4. The method of claim 1 , wherein the mutant enterotoxin and the antigen are co-administered as a chemically conjugated molecule.
5. The method of claim 1 , wherein the mutant enterotoxin and the antigen are co-administered as a chimeric molecule.