Haemonchus contortus vaccine

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Parasitic organism or component thereof or substance...

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4241841, 4241851, 4242661, 514 2, 435 693., 4351723, 4352523, 530350, 530395, 530403, 530822, 530412, 530413, 530416, 536 231, 536 234, 536 235, A61K 39002, C07K 1444, C12N 1530

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055255086

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BRIEF SUMMARY
TECHNICAL FIELD

The invention relates to antigens which confer protective immunity against infection by parasitic nematodes.
The invention also relates to vaccines conferring protective immunity against infection by parasitic nematodes, and to antibodies conferring passive immunity to infection by parasitic nematodes.


BACKGROUND ART

Nematodes (nema - thread; oides - resembling), which are unsegmented roundworms with elongated, fusiform, or saclike bodies covered with cuticle, are virtually ubiquitous in nature, inhabiting soil, water and plants, and are importantly involved in a wide range of animal and plant parasitic diseases.
The roundworm parasites of mammals belong to the phylum Nemathelminthes. The roundworms include the hookworm (e.g. Necator americanus and Ancylostoma duodenale), roundworm (e.g. the common roundworm Ascaris lumbricoides), whipworm (e.g. Trichuris trichiura), and the pinworm or threadworm (e.g. Enterobius vermicularus), as well as Strongyloides stercoralis, Trichinella spiralis (infection in man and pigs), and the filarial worm Wuchereria bancrofti. Other important roundworm parasites include Ancylostoma caninum (infections of man), Strongylus vulgaris (infections of horses), Trichostrongylus colubriformis (infections of sheep), Haemonchus contortus (infections of sheep and goats), Ostertagia ostertagi (infections of cattle), Ascaris suum (infections in pigs), Toxascaris leonia or Uncinaria stenocephala (infections of dogs), Toxocara spp (circulatory infections of man) and Dirofilaria immitis (circulatory infections of cats and dogs).
Even when symptom-free, parasitic worm infections are harmful to the host animal for a number of reasons; e.g. they deprive the host of food, injure organs or obstruct ducts, may elaborate substances toxic to the host, and provide a port of entry for other organisms. In other cases, the host may be a species raised for food and the parasite may be transmitted upon eating to infect the ingesting animal. It is highly desirable to eliminate such parasites as soon as they have been discovered.
More commonly, such infections are not symptom-free. Helminth infections of mammals, particularly by parasitic nematodes, are a source of great economic loss, especially of livestock and pets, e.g. sheep, cattle, horses, pigs, goats, dogs, cats and birds, especially poultry. These animals must be regularly treated with anthelminthic chemicals in order to keep such infections under control, or else the disease may result in anaemia, diarrohea, dehydration, loss of appetite, and even death.
The only currently available means for controlling helminth infections is with the use of anthelminthic chemicals, but these are only effective against resident worms present at the time of treatment. Therefore, treatment must be continuous since the animals are constantly exposed to infection; e.g. anthelminthic treatment with diethylcarbamazine is required every day or every other day most of the year to control Dirofilaria immitis or the dog heartworm. This is an expensive and labor intensive procedure. Due to the widespread use of anthelminthic chemicals, the worms may develop resistance and so new and more potent classes of chemicals must be developed. An alternative approach is clearly desirable.
The development of a vaccine against parasitic nematodes would overcome many of the drawbacks inherent in chemical treatment for the prevention and curing of helminthic infections. The protection would certainly last longer, only the vaccinated animal would be affected, and the problems of toxicity and persistence of residues would be minimized or avoided. Accordingly, there have been attempts, reported in the prior art, to develop such vaccines using parasitic nematodes; unfortunately, they have met with limited success and factors such as material availability and vaccine stability have precluded their large scale use.
These previous attempts are discussed in International Patent Application No. PCT/AU88/00239 (WO 89/00163) and PCT/AU89/00416 (WO 90/03433).
Recent advances in bi

REFERENCES:
Bowie, A. V. et al. Science 247: 1306-1310 (1990).
Kumar, V. et al. Proc. Natl. Acad. Sci 87:1337-1341 (1990).
Ellis, R. W. In: Vaccines Plotkin & Mortimer Eds. W. B. Saunders Co., (1988) pp. 568-515.
Silberstein, O. S. et al. Science 227: 948-50 (1985).
Gold K. M. et al. Mol. Biochem. Parasitol 41: 187-196 (1980).
Young, R. A. et al. Proc. Natl. Acad. Sci. 80: 1194-1198 (1983).
Scopes, R. K. Protein Purfication: Principles and practice Springer-Velag (1987) pp. 221-235.
Gerard, C. et al. "Purification of Glycoproteins" Methods of Enzymology 182:529-534 (1990).
Kennedy, M. W. and Queshi F., "Stage-specific secreted antigens of the parasitic larval stages of the nematode Ascaris", Immunology, vol. 58, 1986, pp. 516-522.
Friedlander et al., "Immunological Aspects of Murine Infection With The Rat Nematode Strongyloides ratti Sandground, 1925, "Z Parasitenkd. 72: 493-509 (1986).
International Journal of Parasitology, vol. 15, No. 2, pp. 129-136, 1985, O'Donnell, Attempts To Probe The Antigens And Protective Immunogens Of Trichostrongylus, etc.

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