Chimeric protein comprising non-toxic pseudomonas exotoxin a and type iv pilin sequences
AssigneeThe United States as represented by the Secretary of the Department of Health and Human Services
InventorDavid J. Fitzgerald
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Abstract
The invention provides chimeric proteins comprising a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, wherein the Type IV loop sequence is inserted within the non-toxic Pseudomonas exotoxin A. The invention also provides polynucleotides encoding the chimeric proteins, and compositions comprising the polynucleotides or the chimeric proteins. The invention also provides methods for using the chimeric proteins, polynucleotides and compositions of the invention.
Claims66
A chimeric protein comprising:
- a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, the Type IV pilin loop sequence being located within the non-toxic Pseudomonas exotoxin A sequence, wherein the chimeric protein is capable of reducing adherence of a microorganism expressing the Type IV pilin loop sequence to epithelial cells, and further wherein the chimeric protein, when introduced into a host, is capable of generating polyclonal antisera that reduce adherence of the microorganism expressing the Type IV pilin loop sequence to the epithelial cells.
A chimeric protein comprising:
- (a) a non-toxic Pseudomonas exotoxin A sequence comprising domain Ia, domain II, and domain III;
- and
- (b) a Type IV pilin loop sequence,
- wherein the Type IV pilin loop sequence is located between domain II and domain III of the non-toxic Pseudomonas exotoxin A sequence.
A polynucleotide encoding a chimeric protein, the chimeric protein comprising:
- a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, the Type IV pilin loop sequence being located within the non-toxic Pseudomonas exotoxin A sequence, wherein the chimeric protein is capable of reducing adherence of a microorganism expressing the Type IV pilin loop sequence to epithelial cells, and further wherein the chimeric protein, when introduced into a host, is capable of generating polyclonal antisera that prevent adherence of the microorganism expressing the Type IV pilin loop sequence to the epithelial cells.
A polynucleotide encoding a chimeric protein, the chimeric protein comprising:
- (a) a non-toxic Pseudomonas exotoxin A sequence comprising domain Ia, domain II, and domain III;
- and
- (b) a Type IV pilin loop sequence,
- wherein the Type IV pilin loop sequence is located between domain II and domain III of the non-toxic Pseudomonas exotoxin A sequence.
A composition comprising a chimeric protein, the chimeric protein comprising:
- a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, the Type IV pilin loop sequence being located within the non-toxic Pseudomonas exotoxin A sequence, wherein the chimeric protein is capable of reducing adherence of a microorganism expressing the Type IV pilin loop sequence to epithelial cells, and further wherein the chimeric protein, when introduced into a host, is capable of generating polyclonal antisera that prevent adherence of the microorganism expressing the Type IV pilin loop sequence to the epithelial cells.
A method for eliciting an immune response in a host, the method comprising the step of administering to the host an immunologically effective amount of a composition comprising a chimeric protein comprising:
- a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, the Type IV pilin loop sequence being located within the non-toxic Pseudomonas exotoxin A sequence, wherein the chimeric protein is capable of reducing adherence of a microorganism expressing the Type IV pilin loop sequence to epithelial cells, and further wherein the chimeric protein, when introduced into the host, is capable of generating polyclonal antisera that prevent adherence of the microorganism expressing the Type IV pilin loop sequence to the epithelial cells.
A method of eliciting an immune response in a host, the method comprising the step of administering to the host an immunologically effective amount of an expression cassette comprising a polynucleotide encoding a chimeric protein comprising:
- a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, the Type IV pilin loop sequence being located within the non-toxic Pseudomonas exotoxin A, wherein the chimeric protein is capable of reducing adherence of a microorganism expressing the Type IV pilin loop sequence to epithelial cells, and further wherein the chimeric protein, when introduced into the host, is capable of generating polyclonal antisera that reduce adherence of the microorganism expressing the Type IV pilin loop sequence to the epithelial cells.
A method of generating antibodies specific for a Type IV pilin loop sequence, comprising introducing into a host a composition comprising a chimeric protein comprising a non-toxic Pseudomonas exotoxin A sequence and a Type IV pilin loop sequence, the Type IV pilin loop sequence being located within the non-toxic Pseudomonas exotoxin A, wherein the chimeric protein is capable of reducing adherence of a microorganism expressing the Type IV pilin loop sequence to epithelial cells, and further wherein the chimeric protein, when introduced into the host, is capable of generating polyclonal antisera that reduce adherence of the microorganism expressing the Type IV pilin loop sequence to epithelial cells.
Dependencies are inferred from the claim text.