Abstract: The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host. The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. The mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.
Type:
Grant
Filed:
December 1, 2015
Date of Patent:
July 18, 2017
Assignees:
INSTITUT PASTEUR, INSTITUTE OF MICROBIOLOGY OF THE ASCR, V.V.I., INSTITUTE OF PHYSIOLOGY OF THE ASCR, V.V.I.
Inventors:
Peter Sebo, Adriana Osickova, Jiri Masin, Catherine Fayolle, Jan Krusek, Marek Basler, Claude Leclerc, Radim Osicka
Abstract: The invention relates to mutant CyaA/E570Q+K860 polypeptides suitable for use as proteinaceous vectors for delivering one or more molecules of interest into a cell, in particular into a cell expressing the CD11b receptor. The invention further relates to polypeptide derivatives suitable for eliciting an immune response in a host. The invention is more particularly directed to polypeptides derived from an adenylate cyclase protein (CyaA) either under the form of a toxin or of a toxoid, which are mutant polypeptides. Said mutant polypeptides are capable of retaining the binding activity of native CyaA to a target cell and preferably of also retaining the translocating activity of native CyaA through its N-terminal domain into target cells and furthermore have a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.
Type:
Application
Filed:
December 1, 2015
Publication date:
March 24, 2016
Applicants:
INSTITUT PASTEUR, INSTITUTE OF MICROBIOLOGY OF THE ASCR, V.V.I., INSTITUTE OF PHYSIOLOGY OF THE ASCR, V.V.I.
Inventors:
PETER SEBO, ADRIANA OSICKOVA, JIRI MASIN, CATHERINE FAYOLLE, JAN KRUSEK, MAREK BASLER, CLAUDE LECLERC, RADIM OSICKA
Abstract: A polypeptide comprises a mutated Bordetella pertussis CyaA (SEQ ID NO:1), Bordetella parapertussis CyaA (SEQ ID NO:7), Bordetella hinzii CyaA (SEQ ID NO:8), or Bordetella bronchiseptica CyaA (SEQ ID NO:9), or a fragment thereof lacking all or part of the N-terminal catalytic domain of the CyaA, or a polypeptide having at least 95% sequence identity with SEQ ID NOS: 1, 7, 8, or 9. The glutamic acid residue at position 570 of SEQ ID NO: 1, 7, 8 or at position 569 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The lysine residue at position 860 of SEQ ID NO: 1, 7, 8 or at position 859 of SEQ ID NO:9 has been substituted by a conservative amino acid residue. The polypeptide retains the binding activity of native CyaA to CD11b expressing cell, and has a pore-forming activity which is reduced or suppressed as compared to that of the native CyaA toxin.
Type:
Grant
Filed:
March 23, 2010
Date of Patent:
December 29, 2015
Assignees:
INSTITUT PASTEUR, INSTITUTE OF MICROBIOLOGY OF THE ASCR, V.V.I., INSTITUTE OF PHYSIOLOGY OF THE ASCR. V.V.I.
Inventors:
Peter Sebo, Adriana Osickova, Jiri Masin, Catherine Fayolle, Jan Krusek, Marek Basler, Claude Leclerc, Radim Osicka