Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Reexamination Certificate
1997-01-21
2001-02-27
Duffy, Patricia A. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
C424S185100, C424S265100, C424S266100, C424S276100, C435S007100, C436S518000, C530S300000, C530S350000
Reexamination Certificate
active
06193971
ABSTRACT:
BACKGROUND OF THE INVENTION
The invention relates to an antigen from the adult stages of the bovine lungworm
Dictyocaulus viviparus
(also termed
D. viviparus
or Dictyocaulus in that which follows), which antigen can be used for the immunodiagnostic detection of lungworm infestation in cattle. In a vaccine, the antigen is able to elicit immune protection against
D. viviparus
.
Lungworms are of great pathogenic and economic importance, particularly in the case of small and large ruminants. Dictyocaulus is the only lungworm which achieves sexual maturity in cattle. It is found throughout the world wherever moderate temperatures of 15-20° C. prevail at least from time to time. In Europe,
D. viviparus
is dispersed endemically in the great river meadows, in high-rainfall coastal regions and also on alpine pastures (R. J. Jörgensen (1980) Vet. Parasitol. 7, 153-167; H. Pfeiffer (1976) Wien. Tierärztl. Mschr. 63, 54-55). In the Netherlands, for example, clinical dictyocaulosis has been observed in more than 77% of calf groups which are maintained on pastures (J. Boch, R. Supperer (1992) Veterinärmedizinische Parasitologie [Veterinary Parasitology], 4th edn., Parey, Berlin, pp. 294-301.)
In calves which are exposed for the first time, the disease (dictyocaulosis) is caused by ingesting third-stage larvae together with the pasture grass. Via the bloodsteam, the larvae arrive at the alveoli of the lungs, which they penetrate in order to reach the air-carrying parts of the lung. In connection with this, lesions are produced which serve as an entry port for secondary infections due to bacteria; the multiplication of bacteria and other microbial pathogens leads to localized or generalized pulmonary inflammations with all the possible sequelae such as pulmonary edema and heart failure (T. Schnieder, A. Bellmer, F.-J. Kaup (1989) Wien. Tierärztl. Mschr. 76:372-476). Breathing is also made substantially more difficult by the presence in the upper airways of adult stages, which lead to obstructions. Diminished increases in weight, or even losses of weight, associated with growth delays are visible consequences of the marked impairment of the general state of health. From time to time, the clinical symptoms worsen dramatically and rapidly lead to death.
Lungworm disease in cattle can be diagnosed from the clinical symptomatology (G. Gräfner (1987) Monatsh. Vet. med. 42:178-181) or from the larvae which are excreted in the feces (J. Boch, R. Supperer (1992)). These options are particularly suitable for diagnosing the disease in an individual animal which is heavily infected. However, for modern large-scale animal husbandry, it is necessary to make epidemiological predictions and risk assessments, which are based on a suitable diagnosis, with regard to the outbreak of a dictyocaulosis when the grazing season is at an advanced stage; i.e. many calves, which may still only be mildly infected, have to be examined in surveys using a reliable and sensitive method. Serological methods are suitable for this purpose (A. Bellmer, T. Schnieder, A. M. Tenter (1989) Proc. 13th Conf. Wrld Ass. Adv. Vet. Parasit., p. 33, Berlin, 7.-11.8.1989). Antigens which have been identified in
Dictyocaulus viviparus
and then isolated and in some cases prepared in recombinant form are used for the serodiagnosis. Pharmaceuticals which are active against adult and juvenile stages can be employed for the curative treatment of dictyocaulosis (e.g. Levamisol®, (pro) benzimidazole, Netomin® and Ivermectin®). These preparations are highly active and are consequently usually able to prevent losses which are due to acute lungworm disease (H. Mehlhorn, D. Düwel, W. Raether (1993) Diagnose und Therapie der Parasitosen von Haus-, Nutz- und Heimtieren [Diagnosis and Therapy of the parasitoses of domestic animals, farm animals and pets]. 2nd edn. Gustav Fischer Verlag, pp. 223-227). Due to their drastic efficacy, the active compounds may not, when being used for a prophylactic/metaphylactic treatment, permit interaction of the parasite with the immune system of the host and, as a consequence, the development and maintenance of a resilient (partial) immunity. The animals are then, while still being unprotected, at the mercy of an infection in the second grazing year (COBS, D. E., S. R. Pitt, J. Förster, M. T. Fox (1987) Res. Vet. Sci. 43:273-275).
Recently, therefore, there have been ever more frequent demands for calves of the first grazing season to be immunized for epidemiological reasons, either by means of a low-grade subclinical infection or by means of vaccination. At present, only one live vaccine, in the form of X-ray attenuated larvae, is available, with this vaccine evoking a basal immunity which has to be maintained by subsequent natural infection (Mehlhorn H., et al., (1993)). If subsequent immunization by means of natural infection is insufficient, breakdowns, associated with coughing and disease, occasionally occur in connection with sudden, massive exposure. Since the vaccine itself only keeps in a refrigerator for about 3 weeks, it must be stored carefully and used rapidly. This procedure prevents any “surface-covering” use; the vaccine is therefore first and foremost reserved for particular endemic regions. Because of the inadequate stability and quality, there is a need to develop defined vaccines (subunit vaccines).
SUMMARY OF THE INVENTION
The object therefore presented itself of removing the cited disadvantages of the current vaccination method by preparing a novel, advantageous vaccine.
It is a further object of the present invention to provide a novel antigenic protein invoking an immunogenic response in cattle and other mammalian species.
It is a further object of this invention to provide a means for producing such proteins recombinantly.
In accomplishing the foregoing objects, there has been provided, an immunogenic protein, DV 18, or an immunogenic fragment thereof, wherein the protein has a molecular weight of between approximately 16000 and 19000 daltons, and has an isoelectric point of between approximately 5.2 and 5.8.
There is further provided, an immunogenic DV 18 protein or a fragment thereof, comprising the amino acid sequences as shown in Table 1.
There is further provided, a DNA molecule which encodes an immunogenic protein, DV 18, or an immunogenic fragment thereof, wherein the protein comprises the amino acid sequences as shown in Table 1.
There is further provided, a recombinant protein which comprises the amino acid sequences as shown in Table 1, or immunogenic variants thereof.
REFERENCES:
patent: 4879213 (1989-11-01), Fox et al.
Jørgensen, R.J., “Epidemiology of Bovine Dictyocaulosis in Denmark,”Vet. Parasitol., vol. 7, pp. 153-167 (1980).
Jacobs, D.E. et al., “Interactions between chemoprophylaxis and immunity to bovine parasitic gastroenteritis and bronchitis: pilot studies using an oxfendazole pulse release bolus,”Res. Vet. Sci., vol. 43, pp. 273-275 (1987).
Tovey, E.R. et al. “Comparison of semi-dry and conventional tank-buffer electrotransfer of proteins from polyacrylamided gels to nitrocellulose membranes,”Electrophoresis, vol. 8, pp. 384-387 (1987).
Boch, J. et al., Veterinarmedizinisch Parasitologie, 4., Aufl. P. Parey, Berlin, Germany, pp. 294-301 (1992).
Mehlhorn, H. et al., “Diagnose und Therapie der Parasitosen von Haus-, Nutz-und Heimtieren,” 2., Aufl. Gustav Fischer Verlag, Stuttgart, Germany, pp. 223-227 (1993).
Grafner, G., “Zum epizootiologischen und jahreszeilichen Verlauf von Ostertagiose-Diktyolaulose-Erkrankungen bei Jungrinderherden in den Jahren 1980 bis 1984 in den nördlichen Weidegebieten der DDR,”Mh. Vet.-Med., vol. 42, pp. 178-181 (1987).
Schnieder, T., et al., “Neuere Erkenntinisse zur Ätiologie, Pathogenese und Bekämpfung der Dictyocaulose,”Wien Tierärztl. Mschr., vo;. 76, pp. 372-376 (1989).
Pfeiffer H., “Zur verzögerten Entwicklung des Rinderlungenwurmes, Dictyocaulus viviparus,”Wien Tierärztl Mschr., vol. 63, pp. 54-55 (1976).
Bellmer, A. et al., “Seroepidemiological Survey on the Occurrence ofDictyocaulus viviparusin Lower Saxony
Hofmann Joachim
Schmid Karlheinrich
Akzo Nobel N.V.
Blackstone William M.
Duffy Patricia A.
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