Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Patent
1993-12-06
1997-10-14
Budens, Robert D.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
4352351, 435237, 4351721, 435 693, C12N 701, C12N 708, C12N 1500, A61K 39265
Patent
active
056769512
DESCRIPTION:
BRIEF SUMMARY
This application is a national phase 371 application of PCT/NL92/00097 filed Jun. 5, 1992.
FIELD OF THE INVENTION
This invention relates to the fields of vaccination and diagnostics in connection with diseases which are caused by pathogens and involves the use of both the classic methods to arrive at a live attenuated vaccine or an inactivated vaccine and the modern methods based on DNA recombinant technology.
More specifically, the invention relates to live attenuated vaccines and inactivated vaccines for protecting animals, especially bovines, against bovine herpesvirus type 1 (BHV-1), these vaccines being so designed that they are not only safe and effective, but also create the possibility of distinguishing infected from non-infected animals in a vaccinated population.
Diagnostic kits which can be used for such a test for distinguishing infected from non-infected animals in a vaccinated population are also an aspect of the present invention.
BACKGROUND OF THE INVENTION
BHV-1, including the infections bovine rhinotracheitis virus (IBRV) and the infectious pustular vulvovaginitis virus (IPVV), plays an important role in the development of respiratory diseases and fertility disorders in bovines. After an acute infection, BHV-1 often reminds present in the host in a latent form. Latent virus can be reactivated under the influence of inter alia stress--which may or may not be accompanied by clinical phenomena--and subsequently excreted. As a consequence, infected cattle must be regarded as lifelong potential spreaders of BHV-1. BHV-1 occurs endemically in an estimated 75% of Dutch cattle farms. Especially older cattle are serologically positive.
There are a number of inactivated ("dead") vaccines and a number of attenuated ("live") vaccines available for inoculation against BHV-1 infections. Inactivated vaccines are prepared by killing the BHV-1 virus, for instance by heat treatment, irradiation or treatment with ethanol or formalin. However, these often give insufficient protection. Attenuated vaccines are prepared by a large number of passages on homologous (bovine) or on heterologous cells such as porcine or canine cells, and sometimes viruses are also treated physically or chemically then. In this way, unknown mutations/deletions develop in the virus genome, which often reduce the disease-producing properties of the virus. Attenuated live vaccines give better protection than inactivated vaccines, inter alia because they present more viral antigens to the immune system of the host. Another important advantage of live vaccines is that they can be administered intranasally, i.e., at the site where the first multiplication of the wild type virus occurs after infection. Yet, live vaccines leave room for improvement. Some live vaccines still seem to possess their abortogenic ability, which becomes manifest in particular after intramuscular administration. Moreover, probably all live vaccines remain latently present in the vaccinated cow. Also, there is a chance that if the vaccine differs only little from the wild-type virus, reversion to virulence will occur. But one of the major problems is that the BHV-1 vaccines cannot prevent infection by wild-type viruses. The result is that vaccinated cattle can also spread wild-type BHV-1.
For a proper BHV-1 control program, it is necessary to have disposal of an efficacious and safe vaccine that can be distinguished from wild-type virus, since the application of an efficacious vaccine can reduce the circulation of BHV-1 considerably and a test which can distinguish between a vaccine and a wild-type virus makes it possible to detect (and then remove) infected cattle in a vaccinated population.
Meanwhile, BHV-1 vaccines have been developed which seem to be safer than conventional vaccines and are distinguishable from wild-type virus. A thymidine kinase deletion mutant has been isolated which is abortogenic to a lesser degree, becomes latent less frequently and cannot be reactivated. Further, using recombinant DNA techniques, a BHV-1 vaccine has been constructed w
REFERENCES:
patent: 4992051 (1991-02-01), Kit et al.
Lugovic et al. Veterinarski Arhiv 55, 241-245, 1985.
Dekkers, et al., "Agricultural Biotechnology in Focus in the Netherlands", Pudoc Wageningen, vol. --, pp. 122-127, (1990).
H. Neidhardt et al -Herpes Simplex Virus Type 1 Glycoprotein E Is Not Indispensable for ViralInfectivity, J. of Virol., vol. 61, No. 2, Feb. 1, 1987, pp. 600-603.
S. Chatterjee et al -A Role for Herpes Simplex Virus Type 1 Glycoprotein E in Induction of Cell Fusion, J. Gen. Virol. (1989), vol. 70, pp. 2157-2162 .
Maes Roger Kamiel
Rijsewijk Franciscus Antonius Maria
van Oirschot Johannes Theodorus
Budens Robert D.
Reeves Julie E.
Stichting Centraal Diergeneeskundig Instituut
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