Chimeric protein comprising non-toxic pseudomonas exotoxin and type IV pilin sequences

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.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application claims priority of U.S. Provisional Application No. 60 / 257,877 filed Dec. 21, 2000, the contents of which is incorporated herein by reference in their entirety.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT [0002] Not Applicable. BACKGROUND OF THE INVENTION [0003] Type IV pilin is the major subunit of the pilus or pili which are filamentous structures covering many microorganisms including bacteria and yeast. Among these microorganisms, many pathogenic species express Type IV pilins, including, e.g., P. aeruginosa, N. meningitides, N. gonorrhoeae, Vibro cholera, and Pasteurella multocidam. The first step in infection with these pathogenic microorganisms is adherence to target cells through the pili. In particular, Type IV pilins of Pseudomonas aeruginosa bind to asialoGM1 receptors on epithelial cells (Saiman et al., J. Clin. Invest. 92(4):1875-80 (1993); Sheth et al., 11 (...

AI Technical Summary

Benefits of technology

[0016] In another aspect, the invention provides 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.

[0017] In another aspect, the invention provides 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.

[0018] In another aspect, the invention provides a

Problems solved by technology

This results in the inhibition of protein synthesis and cell death.

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