# US 6,974,581 B1 · Multi-component vaccine comprising at least two antigens from haemophilus influenzae to protect against disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,974,581 B1 - Document ID: US6974581B1 - Status: Granted - Kind: B1 - Application number: 09/210,995 - Filed: 1998-12-15 - Granted: 2005-12-13 - Earliest claimed: 1998-12-15 - Assignees: Aventis Pasteur Limited - Inventors: Sheena M. Loosmore; Yan-Ping Yang; Michel H. Klein - Web page: https://patentgrep.com/patent/US6974581B1 ## CPC - A61K 39/102: {Pasteurellales, e.g. Actinobacillus}, Pasteurella; Haemophilus - A61P 27/16: Otologicals - A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics - A61P 31/04: Antibacterial agents - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## Abstract A multi-component immunogenic composition confers protection on an immunized host against infection caused by Haemophilus influenzae. Such composition comprises at least two different antigens of Haemophilus influenzae, one of which is an adhesin. High molecular weight (HMW) proteins of non-typeable Haemophilus influenzae enhance 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. The Haemophilus vaccine may be combined with DTP component vaccines to provide a multi-valent component vaccine without impairment of the immunogenic properties of the other antigens. ## Claims ### Claim 1 An immunogenic composition for conferring protection in a host against disease caused by Haemophilus influenzae, which comprises: an analog of Haemophilus influenzae Hin47 protein having a decreased protease activity which is less than about 10% of that of natural Hin47 protein, and a high molecular weight (HMW) protein of a strain of non-typeable Haemophilus influenzae. ### Claim 2 (depends on 1) The composition of claim 1 wherein said HMW protein is present in said composition in an amount which enhances the immune response in the host to the Hin47 protein. ### Claim 3 (depends on 2) The composition of claim 2 wherein said HMW protein is present in the said amount while the individual immunogenicities of the proteins in the composition is not impaired. ### Claim 4 (depends on 1) The composition of claim 1 wherein said analog of Hin47 protein is one in which at least one amino acid of the natural Hin47 protein contributing to protease activity has been deleted or replaced by a different amino acid and which has substantially the same immunogenic properties as natural Hin47 protein. ### Claim 5 (depends on 4) The composition of claim 4 wherein said at least one amino acid is selected from the group consisting of amino acids 91, 121 and 195 to 201 of natural Hin47 protein. ### Claim 6 (depends on 5) The composition of claim 5 wherein Serine-197 is replaced by alanine. ### Claim 7 (depends on 5) The composition of claim 5 wherein Histidine-91 is replaced by alanine, lysine or arginine. ### Claim 8 (depends on 7) The composition of claim 7 wherein Histidine-91 is replaced alanine. ### Claim 9 (depends on 5) The composition of claim 5 wherein Asp-121 is replaced by alanine. ### Claim 10 (depends on 3) The composition of claim 3 wherein said HMW protein is an HMW1 or HMW2 protein of a non-typeable strain of Haemophilus influenzae. ### Claim 11 (depends on 10) The composition of claim 10 wherein the HMW1 and HMW2 proteins are produced recombinantly. ### Claim 12 (depends on 10) The composition of claim 10 wherein said HMW1 and HMW2 proteins are derived from the respective strain of non-typeable Haemophilus influenzae and possess respective molecular weights as set forth in the following Table: Molecular Non-typeable H. influenzae Strain Weight (kDa) 12 JoyC K21 LCDC2 PMH1 15 Mature Protein: HMW1 125 125.9 104.4 114.0 102.4 103.5 HMW2 120 100.9 111.7 103.9 121.9 ### Claim 13 (depends on 1) The composition of claim 1 further comprising an adjuvant. ### Claim 14 (depends on 13) The composition of claim 13 wherein said adjuvant is aluminum hydroxide or aluminum phosphate. ### Claim 15 (depends on 1) The composition of claim 1 comprising about 25 to about 100 μg of the Hin47 protein analog, and about 25 to about 100 μg of the HMW protein. ### Claim 16 (depends on 1) The composition of claim 1 further comprising at least one additional antigenic component for conferring protection against infection caused by another pathogen. ### Claim 17 (depends on 16) The composition of claim 16 wherein said at least one additional antigenic component is selected from the group consisting of diphtheria toxoid, tetanus toxoid, pertussis antigens, non-virulent poliovirus and a conjugate of a tetanus or diphtheria toxoid and a capsular polysaccharide of Haemophilus influenzae. ### Claim 18 (depends on 17) The composition of claim 17 wherein said pertussis antigens are selected from the group consisting of pertussis toxoid, filamentous hemagglutinin, pertactin and agglutinogens. ### Claim 19 (depends on 1) A method of immunizing a host against disease caused by infection with Haemophilus influenzae, including otitis media, which comprises administering to the host an immunoeffective amount of the composition as claimed in claim 1.