Mutant cholera holotoxin as an adjuvant

An antigenic composition comprising

• (a) at least one antigen selected from the group consisting of the Haemophilus influenzae P4 outer membrane proteins the Haemophilus influenzae P6 outer membrane protein, the Haemophilus influenzae adherence and penetration protein (HapS), the Helicobacter pylori urease protein, the Neisseria meningitidis Group B recombinant class 1 pilin (rpilin), the Neisseria meningitidis Group B class 1 outer membrane protein (PorA), the respiratory syncytial virus fusion protein, a rotavirus virus-like particle and the herpes simplex virus (HSV) type 2 glycoprotein D (gD2);
• and
• (b) an effective adjuvanting amount of a mutant cholera holotoxin, wherein the mutant holotoxin has reduced toxicity compared to a wild-type cholera holotoxin, and has an amino acid which replaces the deleted glutamic acid which naturally occurs at position 29 of the mature A subunit of the wild-type cholera holotoxin, wherein said amino acid is other than aspartic acid, and wherein said mutant holotoxin enhances the immune response in a vertebrate host to said antigen.

A method for increasing the ability of an antigenic composition containing at least one antigen from a pathogenic organism selected from the group consisting of a bacterium, a virus, a fungus or a parasite to elicit the immune response of a vertebrate host, which comprises administering to said host an antigenic composition comprising

• (a) at least one antigen from a pathogenic organism selected from the group consisting of a bacterium, a virus, a fungus and a parasite;
• and
• (b) an effective adjuvanting amount of a mutant cholera holotoxin, wherein the mutant holotoxin has reduced toxicity compared to a wild-type cholera holotoxin, and has an amino acid which replaces the deleted glutamic acid which naturally occurs at position 29 of the mature A subunit of the wild-type cholera holotoxin, wherein said amino acid is other than aspartic acid, and wherein said mutant holotoxin enhances the immune response in a vertebrate host to said antigen.

A method of preparing an antigenic composition comprising combining

• (a) at least one antigen from a pathogenic organism selected from the group consisting of a bacterium, a virus, a fungus and a parasite;
• and
• (b) an effective adjuvanting amount of a mutant cholera holotoxin, wherein the mutant holotoxin has reduced toxicity compared to wild-type cholera holotoxin and has a substitution which replaces the glutamic acid which naturally occurs at position 29 of the A subunit of the wild-type cholera holotoxin with an amino acid other than aspartic acid, and wherein said mutant holotoxin enhances the immune response in a vertebrate host to said antigen.