Helicobacter lactoferrin receptor

Details Helicobacter lactoferrin receptor Helicobacter lactoferrin receptor

1997-12-05

2000-07-11

Housel, James C.

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Bacterium or component thereof or substance produced by said...

435 732, 435 6, 4352521, A61K 3902

Patent

active

060868937

DESCRIPTION:

BRIEF SUMMARY
This Application is National Stage Application filed under 35 USC 371 of PCT/FR95/01317 Oct. 9, 1995.
The present invention relates to the prevention and treatment of gastric infections caused by Helicobacter bacteria. The subject of the invention is a newly identified surface protein purified from Helicobacter and its use as a vaccine. This protein is able to bind to lactoferrin of human origin.
Helicobacter pylori is a gram-negative bacterium found at the surface of the gastric mucosa in man. This bacterium is associated with a certain number of gastroduodenal pathologies, for at least some of which it is thought to be the causative pathogen. These pathologies are, in particular, acute or chronic gastritis (inflammation of the mucosa), ulcers (destruction of the mucosa), dyspepsia and certain cancers such as gastric adenocarcinoma.
In this respect, it is already seen to be highly desirable to develop a vaccine for preventing and controlling Helicobacter infections.
Various antigens have already been proposed as potential vaccinating agents: these are, in particular, urease (WO 90/4030), cytotoxin and heat shock protein (WO 93/18150) and adhesins.
However, it is envisaged that, in order to reach maximum efficacy, an anti-Helicobacter vaccine will have to contain more than one antigen. It is therefore necessary to pursue the identification of Helicobacter proteins capable of being employed for this purpose.
The presence of a protein which is capable of binding to human lactoferrin has now been demonstrated in a membrane extract of Helicobacter. Surprisingly, this protein consists of two subunits and may be recognized by monoclonal antibodies which are initially raised against the transferring receptor of Neisseria meningitidis.
Accordingly, the subject of the invention is: having an apparent molecular weight of about 98 kD or of about 70 kD, as defined after migration on SDS-PAGE gel containing about 10% polyacrylamide, and being capable of being substantially purified from a membrane extract of Helicobacter by affinity chromatography on a lactoferrin column; as well as of a Helicobacter infection, this composition comprising, as vaccinating principle, at least one protein according to the invention.
The expression "substantially purified protein of 98 or 70 kD" is understood to mean a preparation of this protein which is free of most of the cell constituents of Helicobacter. Obviously, minor contaminants are not excluded.
A protein according to the invention may be obtained from Helicobacter or may be obtained by a recombinant route by expression of the corresponding DNA fragment, in a heterologous system, bacteria, yeasts or mammalian cells.
A protein according to the invention may advantageously be obtained from H. pylori.
A composition according to the invention may be manufactured conventionally. In particular, a protein according to the invention is combined with a pharmaceutically acceptable adjuvant, diluent or support. A composition according to the invention may be administered via any conventional route used in the field of vaccines, in particular via the oral or parenteral route. The administration may take place as a single dosage intake or a dosage intake repeated one or more times after a certain time interval. The appropriate dosage varies as a function of various parameters, for example according to the individual treated or the mode of administration.


BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A--B: The invention is illustrated below with reference to FIG. 1, which shows the electrophoretic profile on SDS-PAGE gel (10% polyacrylamide) of a preparation eluted from a Sepharose 4B-lactoferrin column, after it has been loaded with a membrane extract from H. pylori, as revealed with Coomassie blue FIG. 1A (column A) and with silver nitrate FIG. 1B (column B). The molecular weight standards are phosphorylase B (94 kD), bovine albumin (67 kD), ovalbumin (43 kD), carbonic anhydrase (30 kD), the trypsin inhibitor isolated from soya (soybean trypsin inhibitor) (20.1 kD) and alphalactalbumin (14.4

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