Immunogenic detoxified mutant
View Patent ↗An immunogenic detoxified protein is provided which comprises the amino acid sequence of subunit A of an E. coli heat labile toxin (LT-A) or a fragment thereof in which at least amino acid Ala-72 of the A subunits mutated, preferably by substitution with Arg. The toxoid is useful as vaccine against an enterotoxigenic strain of E. coli and is produced by recombinant DNA means by site-directed mutagenesis. It is also an effective adjuvant.
1. An immunogenic composition comprising (i) at least one antigen and (ii) a mucosal adjuvant comprising an immunogenic detoxified protein comprising the amino acid sequence of subunit A of an E. coli heat labile toxin (LT-A), wherein amino acid corresponding to Ala-72 of the sequence shown in FIG. 12 (SEQ ID NO:1) in said sequence is substituted with an arginine residue.
2. The immunogenic composition of claim 1 , wherein the mucosal adjuvant further comprises at least one subunit B of an E. coli heat labile toxin.
3. The immunogenic composition of claim 1 , wherein the immunogenic detoxified protein comprises a full-length sequence of subunit A of an E. coli heat labile toxin.
4. The immunogenic composition of claim 1 , wherein the detoxified protein possesses residual toxicity.
5. The immunogenic composition of claim 1 , wherein the mucosal adjuvant comprises the sequence of SEQ ID NO:2.
6. An immunogenic composition comprising (i) a pharmaceutically acceptable carrier (ii) a first immunogenic antigen comprising an immunogenic detoxified protein comprising the amino acid sequence of subunit A of an E. coli heat labile toxin (LT-A), wherein amino acid corresponding to Ala-72 of the sequence shown in FIG. 12 (SEQ ID NO:1) in said sequence is substituted with an arginine residue and (iii) a second immunogenic antigen.
7. The immunogenic composition of claim 6 , wherein the mucosal adjuvant further comprises at least one subunit B of an E. coli labile toxin.
8. The immunogenic composition of claim 6 , wherein the immunogenic detoxified protein comprises a full-length sequence of subunit A of an E. coli heat labile toxin.
9. The immunogenic composition of claim 6 , wherein the detoxified protein possesses residual toxicity.
10. The immunogenic composition of claim 6 , wherein the first immunogenic antigen comprises the sequence of SEQ ID NO:2.