Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Amino acid sequence disclosed in whole or in part; or...
Patent
1994-02-21
1996-01-09
Mosher, Mary E.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Amino acid sequence disclosed in whole or in part; or...
4241921, 4242071, 530324, 530350, 530806, 530221, A61K 3921, A61K 39385, C07K 1415, C07K 1900
Patent
active
054827086
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to an immunogenic fused recombinant protein derived from feline leukaemia virus (FeLV), and to a protective vaccine comprising the immunogenic protein.
BACKGROUND OF THE INVENTION
FeLV is a retrovirus of the sub-family oncovirinae. The virus has a simple genomic organisation with three genes, gag, pol and env, encoding vital proteins.
FeLV occurs in three subgroups, A, B or C, which differ in their env genes. FELV-A is present in every isolate and is efficiently transmitted between cats in nature. Viruses of the other two subgroups arise as variants of FeLV-A in individual cats by recombination of endogenous FeLV env genes (FeLV-B) or mutation within the env gene (FeLV-C). Hence the occurrence of subgroups B or C is dependent upon natural infection of cats with FeLV-A.
FeLV is responsible for several fatal diseases in domestic cats including lymphoid and myeloid leukaemias, fibrosarcomas, anaemia, immunodeficiency, enteritis and reproductive failure. The virus is common in nature: a recent survey in the U.K. indicated that the overall prevalance of infection is approximately 15% of sick cats and 6% in healthy cats. These cats have a persistent infection with viraemia and are a source of infection for susceptible animals. FeLV is transmitted either by contact through the transfer of infectious saliva or prenatally across the placenta.
Following natural or experimental exposure of cats to FeLV, there are two possible outcomes. Cats either develop a persistent, life-long infection or recover. Persistently infected cats have a viraemia while recovered cats have no virus in their blood. Some cats which recover may harbour a latent infection in the bone marrow for several weeks or months before it is eliminated. Recovered cans are immune to FeLV as evidenced by their resistance to subsequent challenge with virus.
Two factors influence the outcome of infection. The first is the age an which a cat is exposed to virus. Kittens up to 14 weeks of age are very susceptible and essentially all can be affected by virus challenge. Older kittens are more resistant so that by 16 weeks of age only about 20% can be infected. The other factor governing susceptibility is dose of virus: high doses lead to persistent viraemia while lower does immunise. The consequences of persistent infection are severe and essentially all viraemic cats die within four years of infection. By contrast recovered cats have a normal life span.
Recovery is due to an immune responsa to the virus. Only antibody responses have been examined in detail. However, it is clear that resistance to reinfection is mediated by virus neutralising antibodies which are directed at the envelope surface glycoprotein the virus, gp70. Attempts have been made to immunise cats against FeLV infection with vaccines containing gp70, some of which have been successful.
European patent specification EP 0377842 describes the production of replication-defective FeLV viral sequences. U.S. Pat. No. 4,794,168 relates to the use of immunogens from FeLV envelope protein P15E in vaccines. European patent specifications 0247904, 0173997 and 0216564, International patent publication WO85/02625 and U.S. Pat. No. 4,789,702 all describe the use of the FeLV envelope protein gp70 or fragments thereof as antigens.
SUMMARY OF THE INVENTION
The present invention is based on the discovery that a fused recombinant protein comprising two regions of the FeLV molecule which are normally non-adjacent, when combined produced an immunogenic determinant capable of inducing anti FeLV antibodies on inoculation into cats. The immunised cats are resistant to challenge with live FeLV.
Thus, the present invention provides an immunogenic fused recombinant protein which comprises: (SEQ ID NO:4) or effective fragment thereof, having fused thereto; from the first protein and capable of stabilising the first protein, such that said fused recombinant protein is immunogenic and protective against FeLV infection.
It has been found that the use of gp70 VR1 pro
REFERENCES:
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patent: 5152982 (1992-10-01), Parkes et al.
Plotkin, S. A. et al. 1988 Vaccines, W. B. Saunders Co., Philadelphia pp. 568-575.
Boswell, P. R. et al. 1988. In: Computational Molecular Biology, ed A. M. Lesk, Oxford Univ. Press, pp. 161-178.
Rohn, J. K. et al. 1994, J. Virol. vol. 68 pp. 2458-2467.
J. Brojatsch, et al.; Feline leukemia virus subgroup C phenotype evolves through distinct alterations near the N terminus of the envelope surface glycoprotein, Proc. Natl. Acad. Sci. USA, vol. 89, pp. 8457-8461 (Sep. 1992).
J. H. Nunberg, et al.; Method to map antigenic determinants recognized by monoclonal antibodies: Localization of a determinant of virus neutralization on the feline leukemia virsu envelope protein pg70, Proc. Natl. Acad. Sci. USA, vol. 81, pp. 3675-3679 (Jun. 1984).
Jarrett James O.
Spibey Norman
Mosher Mary E.
The University Court of the University of Glasgow
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