The present invention relates to a therapeutic and preventive anti-bacterial vaccine complex which possesses a vaccinating power linked to the presence of specific antigens against Helicobacter pylori (previously called Campylobacter pylori), Helicobacter hepaticus, Helicobacter coronari, and nonspecific antigens providing immunomodulation.
(MARSHALL B. J., WARREN Jr., Unidentified curved bacilli in the stomach of the patients with gastritis and peptic ulceration Lancer 1984: i:1311-4)).
(MÉGRAUD F., Helicobacter pylori, the most important bacterium among the mucus bacteria. La letter de l""infectiologue 1993; 8 (suppl. 4): 151-9).
It is well known, in bacteriology, that the surface antigens of the walls, membranes or capsules (combined or free in soluble form in the culture medium) are of a glycoprotein, polypeptide or polysaccharide nature.
Vaccines combining associative factors, such as membrane proteoglycan or polysaccharide substances, extracted from pathogenic microbes, with ribonucleic acid of ribosomal origin (RNA) can be used in the production of acellular vaccines (cf. Inf. and Immunity, 1, 574-82, 1970 and PCT WO 94/22462).
These vaccines use specific antigens corresponding to specifically determined microbial diseases.
However, the antigenicity is essentially linked to the level of RNA (of the ribosomes in particular) in microbial cells, inter alia. Immunocompetent cells (ICC) directly use these RNAs as active carriers.
To produce the complex of the invention, with the Helicobacter bacterial serotype antigen, we coupled preferably by means of covalent bonds, RNA, preferably of ribosomal origin, with an amino acid sequence of glycoprotein nature, preferably present in type III collagen. In humans, collagen represents approximately a third of the proteins in the body. The type III was chosen for its amino acid sequence and its presence in the dermis, the vascular wall and the digestive epithelial mucous membranes.
In our complex, we have used, as stabilizer, cell membrane fractions derived from the same microbes as those which served for the production of the ribosomal RNA. These membrane fractions contain all of the peptidoglycan substances and are known, in addition, as immunity adjuvants.
It is, in addition to Helicobacter pylori, hepaticus and coronari, useful to havexe2x80x94glucopolysaccharide or proteoglycanxe2x80x94membrane fractions derived from various microbial organisms which have served to provide the RNA by extraction of their ribosomes, which microbes are known for their immunogenesis (recruitment of macrophages, activation of T lymphocytes, potentiation of the synthesis of immunoglobulins, secretory IgA""s in particular (11 S), increase in phagocytosis and stimulation of dependent T cells and the like).
This was thus thought of because, in the precise case of the pathogenesis induced by Helicobacter pylori, hepaticus or helmannii, coronari, the body must produce, in addition to the specific humoral immune response, a cellular response in order to make up for the inefficacy of the antibodies in protecting the individual.
It is known that cell-mediated response does not give rise to the production of antibodies, but only to the generation of sensitized lymphoid cells specific for the antigen involved.
The T lymphocytes act by themselves and/or through the cytokines, and either an inflammatory type response or a cytotoxic response is observed.
The pathogenic power of Helicobacter lies in its ability to colonize the gastric mucous membrane, to survive in the gastric juice and to multiply therein in spite of the host""s immune response, and to generate lesions which are sometimes irreversible (adenocarcinoma, gastric lymphoma or MALT xe2x80x9cmucous associated lymphoid tissuexe2x80x9d lymphomas),
(PARSONNET J: Helicobacter pylori and gastric cancer. Gastroenterol Clin North Am 1993, 22:89-104.
WORTHERSPOON A. C., DOGLIONI C., DISS T. C. et al.: Regression of primary low-grade B-cell gastric lymphoma of mucosa associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet 1993; 342:575-7.
MOHANDAS, Helicobacter pylori and lymphoma, N Eng J Med 1994: 331:746-7).
when it is insufficient during injection: resistance to phagocytosis, induction of apoptosis and the like.
(PETERSON P. K., VERHOEF J., SCHMELING D. and QUIE P. G.: Kinetics of phagocytosis and bacterial killing by human polymorphonuclear leucocytes and monocytes, J. Infec. Dis. 136:502-509, 1977.
KIEHLBAUCH J. A., ALBACH R. A., BAUM I. K., CHANG K. P. Phagocytosis of Campylobacter jejuni and its intracellular survival in mononuclear phagocytes, Infect Immun 1985; 48:446-51).
USPTO Backgrounds
USPTO Backgrounds