Mutant forms of cholera holotoxin as an adjuvant
AssigneeWyeth Holdings Corporation
InventorsBruce A. Green, Randall K. Holmes, Michael G. Jobling, Duzhang Zhu
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Abstract
Mutant cholera holotoxins having single or double amino acid substitutions or insertions have reduced toxicity compared to the wild-type cholera holotoxin. The mutant cholera holotoxins are useful as adjuvants in antigenic compositions to enhance the immune response in a vertebrate host to a selected antigen from a pathogenic bacterium, virus, fungus, or parasite, a cancer cell, a tumor cell, an allergen, or a self-molecule.
Claims65
An immunogenic, mutant cholera holotoxin (CT-CRM) comprising an amino acid sequence of subunit A of the wild-type cholera toxin (CT), wherein said subunit A comprises at least a single amino acid substitution in the amino acid position 25 in the A subunit, and wherein the mutant CT-CRM has reduced toxicity compared to said wild-type CT.
An immunogenic, mutant cholera holotoxin (CT-CRM) comprising an amino acid sequence of subunit A of the wild-type cholera toxin (CT), wherein said subunit A comprises at least a single amino acid insertion in the amino acid position 49 in the A subunit, and wherein the mutant CT-CRM has reduced toxicity compared to said wild-type CT.
An immunogenic, mutant cholera holotoxin (CT-CRM) comprising an amino acid sequence of subunit A of the wild-type cholera toxin (CT), wherein said subunit A comprises at least a double amino acid insertion in the amino acid positions 35 and 36 in the A subunit, and wherein the mutant CT-CRM has reduced toxicity compared to said wild-type CT.
An immunogenic, mutant cholera holotoxin (CT-CRM) comprising an amino acid sequence of subunit A of the wild-type cholera toxin (CT), wherein said subunit A comprises at least a single amino acid substitution in the amino acid position 30 and a double amino acid insertion in the amino acid positions 31 and 32 in the A subunit, and wherein the mutant CT-CRM has reduced toxicity compared to said wild-type CT.
An isolated and purified DNA encoding an immunogenic, mutant cholera holotoxin (CT-CRM) comprising a single amino acid substitution wherein the amino acid arginine in the amino acid position 25 in the A subunit is substituted with a tryptophan.
An isolated and purified DNA encoding an immunogenic, mutant cholera holotoxin (CT-CRM) comprising a single amino acid substitution wherein the amino acid arginine in the amino acid position 25 in the A subunit is substituted with a glycine.
An isolated and purified DNA encoding an immunogenic, mutant cholera holotoxin (CT-CRM) comprising a single amino acid insertion wherein the amino acid residue histidine is inserted in the amino acid position 49 in the A subunit between wild-type amino acid positions 48 and 49.
An isolated and purified DNA encoding an immunogenic, mutant cholera holotoxin (CT-CRM) comprising a double amino acid insertion wherein the amino acid residues glycine and proline are inserted in the amino acid positions 35 and 36 in the A subunit between wild-type amino acid positions 34 and 35.
An isolated and purified DNA encoding a immunogenic, mutant cholera holotoxin (CT-CRM) comprising a single amino acid substitution and a double amino acid insertion wherein the amino acid tyrosine in the amino acid position 30 in the A subunit is substituted with a tryptophan, and wherein amino acids alanine and histidine are inserted in the amino acid positions 31 and 32 in the A subunit between wild-type amino acid positions 30 and 31.
A host cell transformed, transduced, infected or transfected with a nucleic acid molecule comprising an isolated and purified nucleic acid sequence encoding an immunogenic, mutant cholera holotoxin of any of claims:
- 1-21, wherein the sequence encoding the immunogenic, mutant cholera holotoxin is operatively linked to regulatory sequences enabling expression of said mutant holotoxin in a host cell.
Dependencies are inferred from the claim text.