Antigens of Leishmania parasites

Details Antigens of Leishmania parasites Antigens of Leishmania parasites

1986-07-31

1991-02-12

Wax, Robert A.

Drug, bio-affecting and body treating compositions

Lymphokine

424 858, 424 88, 43524027, 530387, 530395, A61K 398

Patent

active

049922734

DESCRIPTION:

BRIEF SUMMARY
The invention is relative to new anti-Leishmania monoclonal antibodies and to hybridomes secreting such monoclonal antibodies. It concerns more particularly monoclonal antibodies susceptible to induce a protective activity with regard to a host sensitive to infection by the leishmanias and equally to recognize the polypeptides coming from these parasites and which are themselves recognized by serums obtained from hosts infected by various species of leishmanias. It concerns lastly antigens susceptible of being recognized by these antibodies and the utilization of these antigens for the constitution of vaccine compositions destined for Man or animals, notably dogs.
The leishmanioses encompass a complex group of infections which have in common to be caused by intracellular parasites of the genus Leishmania. One may refer to the preamble of the international patent application PCT/U.S. No. 82/01678, filed the 17th of Nov. 1982 and published under the No. WO83/01785, to have a general review of the different forms which these infections may assume and the different species of Leishmanias which cause them. The development of these infections as much in third world countries as in industrialized countries is all the more worrying since at the present time the means are few for combating the different infections caused by these parasites and to check their extension into new territories. The therapeutic arsenal is limited and there does not exist at present any vaccination able to achieve an effective prevention without secondary complications.
The antigenic diversity of the leishmanias has been demonstrated notably by the utilization of monoclonal antibodies. One will note on this subject, other than the aforementioned international patent application the works realized by D. McMAHON PRATT and John R. DAVID, (1981), Nature, Vol. 291, 581-583; by E. HANDMAN and R. E. HOCKING (1982), Infections and Immunity, 28-33; by E. HANDMAN, H. M. JARVIS and G. F. LITCHELL (1984) Parasite Immunology, 6, 223-233. The overall impression which comes out of the existing literature is precisely the great variety of the monoclonal antibodies which have been made, these monoclonal antibodies ought to permit precise identifications hereafter of the different existing species and sub-species of Leishmanias. Publications describing the protection effects to a living host against certain species of leishmanias are much rarer. One could cite nevertheless the results of in vivo protection by monoclonal antibodies against the promastigotes of Leishmania mexicana which have been obtained by ANDERSON and coll. (1983) The Journal of Immunology, 131, 1616-1618, on the occasion of the implementation of a test called the "Winn assay system". The principle of this test is described in an article by H. J. WINN (1960) published in the "J. of Immunology", Vol. 84, p. 530.
The invention proceeds from a different process. Indeed, it had as its aim the production of monoclonal antibodies (or of compositions based on several types of monoclonal antibodies) which should be capable, on the one hand, of recognizing the antigenic determinants common to the various leishmania species, on the other hand, to involve a protective effect in vivo against these diverse species. Another objective was the isolation of one or several antigens susceptible of inducing in the host to which they may be administered the aquisition of a global immunity, consequently equally a global protection against the different cutaneous, muco-cutaneous and visceral leishmanioses of the Old and New world.
More particularly still, the invention has for its aim to provide a process permitting to conduct the selection of the antibody-secreting hybridomes towards those which will be capable of producing monoclonal antibodies responding to the above-indicated characteristics.
The anti-Leishmania monoclonal antibodies according to the invention are characterized by their capacity to inhibit the infection of sarcomatous cells by promastigote forms of one or more species of Leishmania, when th

REFERENCES:
Monjour, et al., C. R. Acad. Sc. Paris, +.300, Serie III,= No. 9, 1985, pp. 395-398.
Jaffe et al., The Journal of Immunology, vol. 133, No. 1, pp. 440-447 (1984).
Jaffe et al., The Journal of Immunology, vol. 131, No. 4, pp. 1987-1993 (1983).
Handman et al., Chemical Abstracts, vol. 98, p. 273, 157503n (1983).
Sheppard et al., The Journal of Immunology, vol. 131, No. 3, pp. 1496-1503 (1983).
Pratt et al., Nature, vol. 291, No. 5816, pp. 581-583 (1981).
Guesdon et al., Journal of Immunological Methods, vol. 39, pp. 1-13, (1980).
Handman et al., Infection and Immunity, vol. 37, No. 1, pp. 28-33, (1982).
Handman et al., Parasite Immunology, vol. 6, pp. 223-233, (1984).

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