Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Virus or component thereof
Reexamination Certificate
2001-06-08
2002-09-17
Mosher, Mary E. (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Virus or component thereof
C424S201100, C424S202100, C435S235100, C435S236000
Reexamination Certificate
active
06451321
ABSTRACT:
The present invention is concerned with a virus of an infectious bursal disease virus (IBDV) strain, a vaccine against infectious bursal disease (IBD), a method for the preparation of the virus, a method for the preparation of a vaccine and the use of the virus for the manufacture of a vaccine.
Infectious bursal disease virus (IBDV), a member of the birnaviridae family, is endemic in many poultry producing areas. For IBDV, two serotypes exist, serotype 1 and 2. The two serotypes may be differentiated by virus neutralisation (VN) test. Furthermore, subtypes of serotype 1 have been isolated. These so called “variant” viruses of serotype 1 can be identified by cross-neutralisation test (P. D. Lukert and Y. M. Saif, Diseases of Poultry, 9
th
edition, Wolfe Publishing Ltd., Chapter 28, 648-663, 1991) a panel of monoclonal antibodies (Snyder, D. B. et al, Arch. Virol.127, 89-101, 1992) or RT-PCT (Jackwood, D. J. Proceedings of the International Symposium on Infectious Bursal Disease and Chicken Anaemia, Rauischholzhausen, Germany, 155-161, 1994). Some of these subtypes of serotype 1 of IBDV have been described in literature for example: Classical, Variant-E, GLS, RS593 and DS326 strains (Van Loon et al, Proceedings of the International Symposium on Infectious Bursal Disease and Chicken Infectious Anaemia, Rauischholzhausen, Germany, 179-187, 1994).
IBDV causes infectious bursal disease (IBD) also called Gumboro disease, an acute, highly contagious disease in chickens that has lymphoid tissue as its primary target with a selective tropism for cells of the bursa of Fabricius. The morbidity rate in susceptible flocks is high with rapid weight loss and moderate mortality. Chickens that recover from the disease may have immune deficiencies because of the destruction of the bursa of Fabricius, which is essential to the defence mechanism of the chicken. The IBDV causes severe immunosuppression in chickens younger than 3 weeks of age and induces bursal lesions in chicken up to 3 months old.
For many years the disease could be prevented by inducing high levels of antibodies in breeder flocks by the application of an inactivated vaccine, to chickens that had been primed with attenuated live IBDV vaccine. This has kept economic losses caused by IBD to a minimum. Maternal antibodies in chickens derived from vaccinated breeders prevent early infection with IBDV and diminish problems associated with immunosuppression. In addition, attenuated live vaccines have also been used successfully in commercial chicken flocks after maternal antibodies had declined.
Recently, very virulent strains of IBDV have caused outbreaks of disease with high mortality in Europe. The current vaccination program failed to protect chickens sufficiently.
Live classical IBDV vaccines are usually administered to hatched chickens through drinking water, aerosol (coarse spray) or intra-ocular (eye drops). These methods of post-hatch administration have some disadvantages, most importantly they are expensive because of the labour needed for their administration in particular in large broiler flocks.
The use of vaccines as embryo vaccines (so called in ovo vaccines) has been suggested previously (Sharma et al; Avian diseases 29, 1155-1169, 1985).
Embryo vaccination (in ovo vaccination) in principle could be advantageous due to the early age of resistance to the specific disease and the administration of a uniform dose of vaccine, into each egg using semiautomatic machines with multiple injection heads.
Usually conventional vaccines for post-hatch vaccination of birds can not be used for in ovo vaccination. Late stage embryos are highly susceptible to infection with most vaccine viruses examined including those vaccine viruses, which can be safely used in hatched chicken. As it is shown in Example 1 the commercially available IBDV vaccines for intra-ocular, coarse spray and drinking water administration in hatched chicken are not suitable for administration in ovo.
An IBDV vaccine, for in ovo administration was made available as, so called “complex vaccine”. This vaccine is composed of a mixture of an live IBD virus and chicken serum containing a viral neutralising factor (VNF) in order to decrease the pathogenicity of the live virus. (Whifill et al: Proceedings of XIX World's Poultry Congress, Amsterdam, The Netherlands, 453-455, 1992). Other IBDV complex vaccines are commercially available under the trademark Bursaplex® (Embrex Inc.) and Bursamune® (Fort Dodge).
The commercially available complex vaccines have the disadvantage of using a high virulent pathogenic IBDV strain (so called hot strain) which reduces the hatchability of the vaccinated eggs, if used alone and not complexed to a serum containing a virus neutralising factor. The addition of such chicken serum to the live IBD virus strain however, results in higher manufacturing costs for the IBDV vaccine compared to those containing live IBDV strains alone.
The safety and efficacy of a live IBDV complex vaccine and of a live IBDV vaccine was tested after in ovo administration by Jungbäck et al; (Abstracts of XI International Congress of the World Veterinary Poultry Association, Budapest Hungary, 191ff, 1997). The results show, that the efficacy requirements of the European Pharmacopoea were not fulfilled by the tested vaccines after in ovo administration, because more than 10% of the in ovo vaccinated chicken showed strain severe lesions of the bursa of Fabricius after challenge with a pathogenic IBDV strain.
It is therefore the aim of the current invention to provide a safe and efficacious mild strain of IBDV that can be administered in ovo, in the absence of a serum containing virus neutralising factor, without having a negative impact on hatchability of the vaccinated egg and furthermore, to provide a cost effective manufacturing process for a vaccine for protection against IBD.
The present invention provides a virus of an IBDV strain designated as strain 689, a sample of which is deposited at the European Collection of Cell Culture, (ECACC) of Salisbury, Wiltshire, SP4 OJG, United Kingdom under accession No.V00012609. The IBD virus strain 689 according to the invention is distinct from the existing IBDV (vaccine) strains, is safe for in ovo administration, and is able to induce a solid immune response in chickens.
A virus of the IBDV strain 689 refers to viruses derived from a virus as deposited, as well as those progeny viruses derived from a virus as deposited, and obtainable for example, by serial passaging e.g. in embryonated eggs or in cell culture.
IBDV strain 689 was isolated from a chicken bursa of Fabricius from the field showing mild signs of IBDV. The bursa of Fabricius was homogenised and put on chicken embryo fibroblast cells (CEF). After 5 days of incubation a cythopathogen effect (CPE) was visible and characterised as IBDV with poly- and monoclonal antibodies. A second passage was conducted on CEF and this material (passage level 2) was used in Example 3. The IBDV strain 689 was further plaque purified 3 times and a pre seed was prepared followed by a master seed (passage level 7). The master seed virus was used in the Example 2.
The IBDV strain 689 was identified by means of ELISA using monoclonal antibodies (Moab) according to Van Loon et al (Van Loon, A. A. W. M., D. Lütticken and D. B. Snyder. Rapid quantification of infectious bursal disease (IBD) challenge, field or vaccine virus strains. International symposium on infectious bursal disease and chicken infectious anaemia, Rauischholzhausen, Germany, 179-187, 1994).
As can be seen from Example 4, the IBDV strain 689 belongs together with the commercially available IBDV vaccine strain Nobilis Gumboro strain D78 (Intervet International, Boxmeer, The Netherlands) to the classical type of IBDV, because both strains have an identical reaction pattern with the different monoclonal antibodies and are both able to replicate on primary CEF inducing a CPE.
The Examples 2 and 3 show that IBDV strain 689 is able to induce a protective immune response to a challenge with virulent classical IBDV and var
Loon Van Adriaan Antonius Wilhelmus Maria
Mundt Egbert
Akzo Nobel N.V.
Blackstone William M.
Hill Myron G.
Mosher Mary E.
Ramey III William P.
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