Mutant cyaa polypeptides and polypeptide derivatives...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 9/88 (2006.01)

Patent

CA 2755694

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.

L'invention concerne des polypeptides CyaA/E570Q+K860 mutants appropriés pour être utilisés en tant que vecteurs protéiques destinés à distribuer une ou plusieurs molécules d'intérêt dans une cellule, en particulier dans une cellule exprimant le récepteur CD11b. L'invention concerne également des dérivés de polypeptides appropriés pour déclencher une réponse immunitaire chez un hôte. L'invention concerne plus particulièrement des polypeptides dérivés d'une protéine d'adénylate cyclase (CyaA) sous la forme d'une toxine ou d'une anatoxine, qui sont des polypeptides mutants. Lesdits polypeptides mutants sont capables de maintenir l'activité de liaison d'une CyaA native sur une cellule cible, sont également capables de préférence de maintenir l'activité de translocation d'une CyaA native via son domaine N-terminal dans des cellules cibles, et présentent en outre une activité de formation de pores qui est limitée ou supprimée par rapport à celle de la toxine CyaA native.

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