Chemistry: molecular biology and microbiology – Vector – per se
Patent
1995-09-12
2000-01-11
Achutamurthy, Ponnathapura
Chemistry: molecular biology and microbiology
Vector, per se
4241391, 4241501, 4241641, 4242561, 4241851, 4241901, 4241921, 42419711, 435 693, 435 9141, 4352523, 514 44, 530350, 536 231, 536 237, A61K 39102, C07H 2104, C07K 14285, C12N 1531
Patent
active
06013514&
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The present invention is related to the field of molecular genetics and is particularly concerned with the cloning of an outer membrane protein D15 of Haemophilus.
BACKGROUND OF THE INVENTION
Haemophilus influenzae type b (Hib) is a major cause of bacterial meningitis in children under the age of five years. Protective antibodies to the disease are induced by the capsular polysaccharide of the organism and a vaccine was developed that utilises the purified polyribosyl ribitol phosphate (PRP) as the antigen. This vaccine provides 90% protection in adults and in children over 24 months of age, but was ineffective in children under 24 months Zangwill et al 1993 (The references are identified in a list of reference at the end of this disclosure). Like other polysaccharide antigens, PRP does not induce the proliferation of T-helper cells, and re-immunisation fails to elicit either a booster response or an increase in memory cells. Conjugation of the PRP polysaccharide with protein carriers confers T-cell dependent characteristics to the vaccine and substantially enhances the immunologic response to the PRP antigen. Currently, there are four PRP-carrier conjugate vaccines available. These are vaccines based upon H. influenzae type b capsular polysaccharide conjugated to diphtheria toxoid, tetanus toxoid, or Neisseria meningaitidis outer membrane protein (reviewed in Zangwill et al 1993).
However, the current Haemophilus conjugate vaccines only protect against meningitis caused by Haemophilus influenzae type b. They do not protect against other invasive typeable strains (types a and c) and, more importantly, against non-typeable (NTHi) strains which are a common cause of postpartum and neonatal sepsis, pneumonia and otitis media. In the United States alone, treatment of otitis media costs between 1 and 2 billion dollars per year for antibiotics and surgical procedures, such as tonsillectomies, adenoidectomies and insertion of tympanostomy tubes. To achieve universal protection against H. influenzae related diseases in the 2 to 6 month age group and certain high risk groups, the provision of conserved, cross-reactive non-capsular H. influenzae immunogens is desirable. Methods for inducing immunity against disease are constantly improving and there is presently a move to use subunits and better defined materials as antigens. This is being undertaken to minimise or eliminate potential side-effects caused by certain native immunogens, while preserving their immunogenicity to confer protection against the disease. Therefore, it would be very attractive to develop a universal vaccine against Haemophilus using cross-reactive outer membrane proteins, fragment, analogs, and/or peptides corresponding thereto as protective antigens. Such antigens may be incorporated into the conventional H. influenzae type b conjugate vaccines as additional immunogens or used as autologous carriers for H. influenzae capsular polysaccharides. A high molecular weight outer membrane protein D15 found in non-typeable and type b stains of H. influenzae has been identified as a cross-reactive antigen (Thomas et al., 1990). D15 appears to be cell surface-exposed in its natural state and exhibits a molecular mass of about 80 kDa as judged by SDS-PAGE analysis. It would be desirable to provide the sequence of the DNA molecule that encodes this D15 outer membrane protein and peptides corresponding to portions thereof for diagnosis, immunization and the generation of diagnostic and immunological reagents. The diseases caused by Haemophilus are serious and improved methods for preventing, detecting and treating diseases such as otitis media, epiglottitis, pneumonia, and tracheobronchitis, are required.
SUMMARY OF THE INVENTION
The present invention is directed towards the provision of purified and isolated nucleic acid molecules comprising at least a portion coding for a D15 outer membrane protein of a species of Haemophilus. The nucleic acid molecules comprising at least a portion coding for D15 outer membrane protein are use
REFERENCES:
patent: 4888170 (1989-12-01), Curtis
Loeb, M.R. et al--Outer Membrane Protein Composition in Disease Isolates of Haemophilus influenzae: Pathogenic and Epidemiological Implications--Inf. and Imm. Dec. 1980, pp. 709,717.
Barenkamp, S.J. et al--Subtyping Isolates of Haemophilus influenzae Type b by Outer-Membrane Protein Profiles--J. Of Inf. Diseases, vol. 143, No. 5, May 1981.
Gulig, P.A., et al--Antibody Response of Infants to Cell Surface-Exposed Outer Membrane Proteins of Haemophilus influenzae type b After Systemic Haemophilus Disease--Inf. and Immunity, Jul. 1982, pp. 82-88.
Vachon V.--Transmembrane Permeability Channels across the Outer Membrane of Haemophilus influenzae J. of Bacteriology, Type b--Jun. 1985, pp. 918-924.
Thomas W. et al--Molecular Cloning of DNA Coding for Outer Membrane Proteins of Haemophilus Type b--Inf. and Imm. Jun. 1986, pp. 812-817.
Thomas et al. "Expression in Escherichia coli of a High-Molecular-Weight . . . " Infection and Immunity 58(6), Jun. 1990, pp. 1909-1913.
Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy, Dec. 7, 1995.
Coglan. New Scientist, Nov. 25, 1995, pp. 14-15.
Chong Pele
Klein Michel
Loosmore Sheena
Sia Dwo Yuan Charles
Thomas Wayne
Achutamurthy Ponnathapura
Bui Phuong T.
Connaught Laboratories Limited
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