Connaught Laboratories Limited

Aventis Pasteur Limited

Other

Sanofi Pasteur Inc.

Yan-Ping Yang

Michel Henri Klein

Sheena M Loosmore

Pele Chong

Robin E Harkness

Anthony Bernard Schryvers

Raymond P Oomen

Andrew D Murdin

Scott Gray-Owen

Lisa E Myers

Run-Pan Du

Ali Kandil

Lucy Gisonni

Raafat Emil Fahim

Michel H Klein

Raafat Emil Fahmy Fahim

Quijun Wang

Ken Sasaki

Robert S Munson, Jr

Patrick McVerry

Susan Grass

Ursula McGuiness

Dwo Yan Charles Sia

Recombinant production of Hia protein, in full-length and N-terminally truncated forms, of non-typeable strains of, is described. The nucleic acid and deduced amino acid sequences of Hia genes of various strains of non-typeable and type calso are described.

[object Object]

Purified and isolated nucleic acid molecules are provided which encode Tbp2 proteins ofstrains M35, 3 and LES1. The nucleic acid sequence may be used to produce recombinant Tbp2 proteins of the strain offree of other proteins of thestrain for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecules may be used in the diagnosis of infection.

Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain ofor a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Transferrin receptor genes

Expression vectors are described which permit the recombinant expression of proteins which essentially contain, in addition to nucleic acid encoding the recombinant protein, nucleic acid encoding a non-proteolytic analog ofHin47 protein, with or without leader sequence, or nucleic acid encoding high molecular weight proteins of non-typeable, which are hmwB, hmwC or hmwBC.

Co-expression of recombination proteins

A multi-component immunogenic composition confers protection on an immunized host against infection caused by. Such composition comprises at least two different antigens of, one of which is an adhesin. High molecular weight (HMW) proteins of non-typeableenhance the immune response in a host to a non-proteolytic analog of Hin47 protein in such immunogenic compositions with one component not impairing the immunogenicity of the other. Thevaccine may be combined with DTP component vaccines to provide a multi-valent component vaccine without impairment of the immunogenic properties of the other antigens.

Protective high molecular weight (HMW) proteins are produced recombinantly by expression fromby using a promoter effective inand a nucleic acid molecule which contains a modified operon of a non-typeable strain of Haemophilus. The modified operon contains the portion only of the A region which encodes the mature HMW protein and the complete B and C regions of the operon. Enhanced levels of expression of the HMW proteins can be achieved by including thecer gene, a further copy of the portion of the A region of the operon encoding the mature protein or both in the expression vector. Nucleotide and deduced amino acid sequences of the hmw1 and hmw2 genes and HMW1 and HMW2 proteins, respectively of several non-typeablestrain have been identified.

Protective recombinant Haemophilus influenzae high molecular weight proteins

Purified and isolated nucleic acid molecules are provided which encode transferrin receptor proteins of Moraxella, such as or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce recombinant transferrin receptor proteins Tbp1 and Tbp2 of the strain of Moraxella free of other proteins of the Moraxella strain for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection.

Transferrin receptor genes of Moraxella

Transferrin receptor of moraxella

Protective high molecular weight (HMW) proteins are produced recombinantly by expression from by using a promoter effective in and a nucleic acid molecule which contains a modified operon of a non-typeable strain of Haemophilus. The modified operon contains the portion only of the A region which encodes the mature HMW protein and the complete B and C regions of the operon. Enhanced levels of expression of the HMW proteins can be achieved by including the cer gene, a further copy of the portion of the A region of the operon encoding the mature protein or both in the expression vector. Nucleotide and deduced amino acid sequences of the hmw1 and hmw2 genes and HMW1 and HMW2 proteins, respectively of several non-typeable strain have been identified.

A multi-valent immunogenic composition confers protection on an immunized host against infection caused by both and . Such composition comprises at least four antigens comprising at least one antigen from , and at least one antigen from . Three of the antigens are adhesins. High molecular weight (HMW) proteins and adhesin (Hia) proteins of non-typeable Haemophilus and a 200 kDa outer membrane protein of comprise the adhesin components while the other antigen is a non-proteolytic analog of Hin47 protein. Each component does not impair the immunogenicity of the others. The multi-valent immunogenic composition may be combined with DTP component vaccines, which may also include non-virulent poliovirus and PRP-T, to provide a component vaccine without impairment of the immunogenic properties of the other antigens.

Multi-component vaccine to protect against disease caused by Haemophilus influenzae and Moraxella catarrhalis

Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbp1 or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Purified and isolated nucleic acid is provided which encodes a transferrin receptor protein of a strain of Haemophilus or a fragment or an analog of the transferrin receptor protein. The nucleic acid sequence may be used to produce peptides free of contaminants derived from bacteria normally containing the Tbp1 or Tbp2 proteins for purposes of diagnostics and medical treatment. Furthermore, the nucleic acid molecule may be used in the diagnosis of infection. Also provided are recombinant Tbpl or Tbp2 and methods for purification of the same. Live vectors expressing epitopes of transferrin receptor protein for vaccination are provided.

Haemophilus transferrin receptor genes

A multi-component immunogenic composition confers protection on an immunized host against infection caused by . Such composition comprises at least three different antigens of , two of which are adhesins. High molecular weight (HMW) proteins and adhesin (Hia) proteins of non-typeable comprise the adhesin components while the other antigen is a non-proteolytic analog of Hin47 protein. Each component does not impair the immunogenicity of the others. The Haemophilus vaccine may be combined with DTP component vaccines, which may contain inactivated poliovirus, including type 1, type 2 and/or type 3, and/or a conjugate of a capsular polysaccharide of and tetanus or diphtheria toxoid, including PRP-T, to provide a multi-valent component vaccine without impairment of the immunogenic properties of the other antigens.

Multi-component vaccine comprising at least three antigens to protect against disease cased by Haemophilus influenzae

Immunogenic conjugate molecules comprising at least a portion of a capsular polysaccharide of a Streptococcus strain linked to at least a portion of an outer membrane protein of a Haemophilus strain are provided in which the immunogenicity of the capsular polysaccharide is increased. Particularly capsular polysaccharide from,are linked to an outer membrane protein of a,strain, which protein may be the P1, P2 or particularly the P6 outer membrane protein. Conjugate molecules comprising the P6 protein linked to a capsular polysaccharide from an encapsulated pathogen other than Streptococcus also are described, in which the immunogenicity of the capsular polysaccharide is enhanced. Such conjugate molecules may be incorporated into immunogenic compositions for protecting a host against disease caused by the Streptococcus strain and preferably also the Haemophilus strain. The conjugate molecules and antibodies specific for the capsular polysaccharide or specific for the outer membrane protein may be employed in diagnostic procedures and kits. A process for individually isolating P1, P2 and P6 outer membrane proteins from a Haemophilus strain also is provided.

Immunogenic conjugate molecules

An isolated and purified non-denatured transferrin receptor protein of a Moraxella strain, particularly,, has an apparent molecular mass of about 80 to about 90 kDa, as determined by SDS-PAGE. The transferrin receptor protein or a fragment analog thereof is useful in diagnostic applications and immunogenic compositions, particularly for in vivo administration to a host to confer protection against disease caused by a strain of Moraxella.

Growing community of inventors

Willowdale, Canada

Yan-Ping Yang