Recombinant attenuated clostridium organisms and vaccine
AssigneeIntervet Inc.
InventorsMark D. Cochran, Gary R. Petersen, Stephen V. Lair, Richard M. Synenki
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Abstract
The present invention discloses attenuated Clostridium perfringens organisms that express a substantially nontoxic alpha-toxin. The expressed alpha-toxin is a deletion mutein that relative to the alpha-toxin of the mature alpha-toxin of Clostridium perfringens strain 13, is missing at least nine consecutive amino acid residues including His68. The present invention also discloses attenuated organisms that encode the muteins, as well as the use of such attenuated organisms as vaccines.
Claims29
An attenuated Clostridium perfringens organism constructed by integrating a nucleic acid molecule that encodes a substantially nontoxic mutein of Clostridium perfringens alpha-toxin into a chromosome of a non-attenuated Clostridium perfringens organism;
- wherein the substantially nontoxic mutein alpha-toxin comprises the amino acid sequence of SEQ ID NO:
- 3 minus at least 9 consecutive amino acid residues, with no more than 24 consecutive amino acid residues deleted;
- wherein one of the deleted amino acid residues is His68;
- and
- wherein the attenuated Clostridium perfringens organism is substantially nontoxic due to a lack of a functional wild-type plc gene.
A Clostridium perfringens organism that is CPERF/ΔαToxin 365-054 having ATCC Deposit No. PTA7364.
A Clostridium perfringens organism that is CPERF/ΔαToxin 365-053 having ATCC Deposit No. PTA7365.
An isolated attenuated Clostridium perfringens organism constructed by integrating a nucleic acid molecule that encodes a substantially nontoxic mutein of Clostridium perfringens alpha-toxin into a chromosome of a non-attenuated Clostridium perfringens organism;
- wherein the substantially nontoxic mutein alpha-toxin comprises the amino acid sequence of SEQ ID NO:
- 3 in which 9 consecutive amino acid residues have been deleted;
- wherein one of the deleted amino acid residues is His68;
- and
- wherein the attenuated Clostridium perfringens organism is substantially nontoxic due to a lack of a functional wild-type plc gene.
An attenuated Clostridium perfringens organism constructed by integrating a nucleic acid molecule that encodes a substantially nontoxic mutein of Clostridium perfringens alpha-toxin into a chromosome of a non-attenuated Clostridium perfringens organism;
- wherein the substantially nontoxic mutein alpha-toxin comprises the amino acid sequence of SEQ ID NO:
- 3 in which His68 is deleted together with an additional 4 to 60 flanking amino acid residues;
- and
- wherein the attenuated Clostridium perfringens organism is substantially nontoxic due to a lack of a functional wild-type plc gene.
Dependencies are inferred from the claim text.