Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for...
Patent
1996-04-26
1999-03-23
Hutzell, Paul K.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
435 691, 435 693, 435212, 4242651, 4242661, 424 941, 4241841, 424 9464, 4241401, 4241511, 530350, 530403, 530412, 530413, 530414, 530416, 536 231, 536 232, 536 235, 536 237, 514 2, 514 21, C12N 948, A61K 3848
Patent
active
058858148
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/01274 filed Jun. 14, 1994 which claims priority under 35 U.S.C., 119 of Great Britain application 9312324.8 filed Jun. 15, 1993.
The invention relates to the use of a class of serine proteases as protective antigens against helminth parasites.
Each species of domestic animal can be parasitised by a number of different species of helminths, a process which usually causes disease. For example, the parasitic trematode Fasciola hepatica is known to be the cause of the economically important disease fascioliasis in ruminants, such as cattle and sheep. The parasite enters the mammalian host by penetrating the gut wall and spends approximately seven weeks feeding on and burrowing through the liver mass before migrating into the bile duct. Following infection, development of immunity in the host can be poor and resistance to reinfection in already infected hosts may be only partial or non-existent. Other parasitic flukes include Fasciola gigantica and Dicrocoelium spp. and also Paramphistomum spp.
Problems are also caused by nematodes such as hookworms (e.g. Necator, Ancylostoma, Uncinaria and Bunostomum spp.).
Of the blood feeding nematodes the genus Haemonchus causes anaemia and weight loss and if untreated frequently leads to death. Animals infected with the related non-blood feeding nematode Ostertagia similarly fail to thrive and may die if untreated.
Other parasitic worms of economic importance include the various species of the following helminth genera: Trichostrongylus, Nematodirus, Dictyocaulus, Cooperia, Ascaris, Dirofilaria, Trichuris and Strongylus. In addition to domestic livestock, pets and humans may also be infected, not infrequently with fatal results and helminth infections and infestations thus pose a problem of considerable worldwide significance.
Control of helminth parasites of grazing livestock currently relies primarily on the use of anthelmintic drugs combined with pasture management. Such techniques are often unsatisfactory, firstly because anthelmintic drugs may have to be administered frequently, secondly because resistance against anthelmintic drugs is--becoming increasingly widespread and thirdly because appropriate pasture management is often not possible on some farms and even where it is, it can place constraints on the best use of available grazing.
Numerous attempts have been made to control helminth parasites of domestic animals by immunological means. With very few exceptions (e.g. the cattle lungworm, Dictyocaulus viviparus) this has not proved possible.
A vaccine against F.hepatica has been proposed in W090/08819 comprising a glutathione-S-transferase from F.hepatica as antigenic material.
Bennett (UK Patent No. 2169606B) extracted various antigens from Fasciola organisms by a process which separates antigens specific to the juvenile stage from antigens present throughout the juvenile and adult stages.
Furthermore crude in vitro excretory/secretory (E/S) products can under some circumstances confer immunity on rats (Rajasekariah et al, Parasitol. 79 (1979), p. 393-400).
It has now been found that F.hepatica excretory/secretory products contain a novel protein having a dipeptidyl peptidase (DPP) type of activity described in more detail hereinafter. This discovery opens up the possibility of vaccines against F.hepatica and other helminths based on the use of the novel enzyme as an antigen and/or corresponding enzymes produced by other helminth parasites.
Accordingly a first aspect of the present invention provides a vaccine for use in combating a parasitic infestation of helminths in a mammal wherein the antigenic material comprises a serine protease having dipeptidyl peptidase-like activity, in at least partially purified form, or an antigenic fragment or epitope thereof, together with a carrier and/or adjuvant.
The invention also provides a method of combating a parasitic infestation of helminths in a mammal comprising administering to said mammal a vaccine according to the invention as hereinbefore defined in an amount effective to com
REFERENCES:
patent: 4879213 (1989-11-01), Fox et al.
Plotein et al. (1988) Vaccines, WB Saunders Co., Philadelphia pp. 570-571.
Burgess et al (1990) J. Cell Biol. vol. 111, 2129-2138 Lehuizer Biochemistry, 2nd ed. Worth Publishers Inc. p. 63.
Lazen et al. (1988) Mol. and Cell Biol. vol. 8(3), 1247-1252.
Sea-Hui (1988) J. Biol-Chem. 263, 6613-18.
Bogitsh et al (1983) J. Parasital vol. 69, 106-10.
Waderl. et al (1986) IEBS Lett. vol 209, 330-334.
Andrews Stuart J.
Dalton John P.
Hutzell Paul K.
Mallinckrodt Veterinary, Inc.
Masood Khalid
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