Modified immunogenic pneumolysin, compositions and their use...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/31 (2006.01) A61K 39/09 (2006.01) A61K 39/395 (2006.01) A61K 47/48 (2006.01) C07K 14/00 (2006.01) C07K 14/315 (2006.01)

Patent

CA 2297374

This invention relates to modified pneumolysin polypeptides that retain the immunogenic nature of pneumolysin but have reduced or undetectable hemolytic activity compared to native pneumolysin. The invention also provides a method for generating novel pneumolysin variants with these desired characteristic properties. The invention also provides immunogenic compositions useful as pharmaceutical compositions including vaccines in which non-toxic, modified pneumolysin is used to stimulate protective immunity against Streptococcus pneumoniae. The vaccines may be compositions in which the modified pneumolysin in conjurated to bacterial polysaccharides or may be carried on an attenuated viral vector. In addition, the invention also provides a method of using the non-toxic, modified pneumolysin toxoid in order to stimulate antibodies against Streptococcus pneumoniae in a treated individual which are then isolated and transferred to a second individual, thereby conferring protection against Streptococcus pneumoniae in thesecond individual.

Cette invention concerne des polypeptides pneumolysine modifiée qui conservent la nature immunogène de la pneumolysine mais présente une activité hémolytique réduite ou non détectable comparé à la pneumolysine naturelle. Cette invention concerne également un procédé permettant de produire de nouveaux variants de pneumolysine présentant les propriétés caractéristiques désirées; ains ique des compositions immunogènes utiles an tant que compositions pharmaceutiques comprenant des vaccins dans lesquels on utilise de la pneumolysine modifiée non toxique pour stimuler la protection immunitaire contre Streptococcus pneumoniae. Les vaccins peuvent être des compositions dans lesquelles la pneumolysine modifiée est conjuguée à des polysaccharides bactériens ou bien dans lesquels la pneumolysine modifiée peut être transportée sur un vecteur viral atténué. En outre cette invention concerne également un procédé d'utilisation du toxoïde de pneumolysine modifiée non toxique afin de stimuler les anticorps contre Streptococcus pneumoniae chez un individu traité, ces anticorps étant ensuite isolés et transférés à un deuxième individu pour conférer ainsi une protection contre Streptococcus pneumoniae chez le deuxième individu.

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