Analog of haemophilus hin47 with reduced protease activity

Details Analog of haemophilus hin47 with reduced protease activity Analog of haemophilus hin47 with reduced protease activity

C - Chemistry, Metallurgy

12

N

C12N 15/57 (2006.01) A61K 39/102 (2006.01) C07K 14/285 (2006.01) C07K 17/02 (2006.01) C07K 19/00 (2006.01) C12N 1/21 (2006.01) C12N 9/50 (2006.01) C12N 9/52 (2006.01) C12N 15/31 (2006.01) G01N 33/569 (2006.01) G01N 33/573 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2171611

An isolated and purified analog of Haemophilus influenzae Hin47 protein has a decreased protease activity which is less than about 10% of that of natural Hin47 protein and preferably substantially the same immunogenic properties as natural Hin47 protein. An isolated an purified nucleic acid-molecule encoding the Hin47 analog may be provided in a recombinant plasmid which may be introduced into a cell which is grown to produce the Hin47 analog. Immunogenic compositions comprising the Hin47 analog and the encoding nucleic acid may be formulated as vaccines for in vivo administration to a host, including a human, to confer protection against diseases caused by a bacterial pathogen, including Haemophilus species, such as Haemophilus influenzae, that produces Hin47 protein or a protein capable of inducing antibodies in the host specifically reactive with Hin47 protein. The Hin47 analog and the encoding nucleic acid also may be employed in diagnostic applications.

Analogues isolés et purifiés de la protéine Haemophilus influenzae Hin47 présentant une activité protéase réduite (inférieure à environ 10 % de celle de la protéine naturelle) et de préférence sensiblement les mêmes propriétés immunogènes que la Hin47 naturelle. Les analogues préférés présentent des mutations au niveau des positions Ser197, His91 et/ou Asp121, et peuvent être utilisés comme des protéines chimères avec d'autres molécules immunogènes. L'invention porte également sur un acide nucléique codant lesdits analogues, des plasmides recombinés et des cellules hôtes transformées contenant ledits gènes modifiés, des compositions immunogènes comprenant les analogues de Hin47 ou leur acide nucléique ainsi que sur leur utilisation à des fins prophylactiques, diagnostiques ou de vaccination.

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