Mutant CyaA polypeptides and polypeptide derivatives suitable for the delivery of immunogenic molecules into a cell

US9222143B2 · kind B2 · utility

Assignees

• INSTITUT PASTEUR · FR
• INSTITUTE OF MICROBIOLOGY OF THE ASCR, V.V.I. · CZ
• INSTITUTE OF PHYSIOLOGY OF THE ASCR, V.V.I. · CZ

Inventors

• Peter Sebo · Praha, CZ
• Adriana Osickova · Praha, CZ
• Jiri Masin · Úvaly, CZ
• Catherine Fayolle · Épinay-sur-Orge, FR
• Jan Krusek · Praha, CZ
• Marek Basler · Praha, CZ
• Claude Leclerc · Paris, FR
• Radim Osicka · Praha, CZ

Key dates

• Filing date: Mar 23, 2010
• Grant date: Dec 29, 2015
• Expiry date: Mar 23, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Y406/01001
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

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.