Chicken anemia virus mutants and vaccines and uses based on the

Details Chicken anemia virus mutants and vaccines and uses based on the Chicken anemia virus mutants and vaccines and uses based on the

1995-11-30

2000-06-06

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...

4242041, A61V 3912

Patent

active

060715200

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to novel proteins and/or polypeptides of the Chicken Anemia Virus. Besides, it relates to vaccines and compositions for preventing or treating virus infections in poultry, in particular infections with the Chicken Anemia Virus (CAV).
In particular, the invention relates to vaccines that are less pathogenic than the CAV itself but yet lead to the generation of neutralizing antibodies in the immunized animal.
Besides, the invention relates to compositions containing antibodies against parts of the CAV for controlling infections with CAV. Also anti-idiotype antibodies which possess an immunogenicity corresponding with the antigen are a subject of the invention.
The invention also relates to antibodies for the detection or control of CAV infections. Also diagnostic test kits for the detection of CAV will be described.
The invention further relates to recombinant DNA molecules derived from CAV, which code for at least an immunogenic part of a CAV protein and host cells transfected with such recombinant DNA molecules. Vaccines based on these host cells are made possible by this invention.
Also so-called living virus vaccines, in which a piece of DNA coding for at least an immunogenic part of a CAV protein is brought into a virus infectious to the desired host, are a subject of the invention.
Processes for the prophylaxis or control of CAV infections, in particular in chickens, and processes for the preparation of recombinant parts of CAV comprising sequences, and processes for the preparation of vaccines are also subjects of the invention.
Besides, the invention relates to uses of the proteins of the CAV in the induction of apoptosis (programmed cell death). In particular, the proteins (polypeptides) can be used in the induction of apoptosis in tumor cells.
Besides, the proteins according to the invention can also be used in the elimination of other undesired cell populations, such as autoimmune reactive T cells in autoimmure diseases, such as rheumatoid arthritis, lupus, etc.
The invention further provides for the induction of cell death by means of gene therapy. Processes for preparing these therapeutics and processes for treatment therewith are also subjects of the invention.
The Chicken Anemia Virus (CAV) is a recently characterized DNA virus (Noteborn and De Boer. 1990). It belongs to a new virus family. In young chickens CAV causes anemia by destruction of erythroblastoid precursor cells and immune deficiency by depletion of thymocytes. Lesions occur in the spleen and liver (Jeurissen et al., 1989). A recent study has shown that the depletion of thymocytes is caused via apoptosis induced by CAV (Jeurissen et al., 1992b).
Gelderblom et al. (1989) and Todd et al. (1990) have shown by means of electron microscopic studies that CAV particles have a T3 icosahedron symmetry and a diameter of 23-25 nm. The CAV particles concentrate after equilibrium sedimentation at a density of 1.33-1.34 g/ml in CsCl.
Todd et al. (1990) have shown that isolated virus particles contain only one protein having a molecular weight of 50 kDa. The single-stranded DNA in the CAV particles is in the form of a circular minus strand (Gelderblom et al.; Todd et al., 1990; Noteborn et al., 1991). The replicative DNA intermediary was cloned and fully sequenced. The CAV genome is 2319 nucleotides long. On the basis of the genome structure and the DNA sequence the virus cannot be placed into one of the known virus families (Noteborn et al., 1991; Todd et al., 1991). The CAV genome contains three large, partially or completely overlapping reading frames coding for possible proteins having molecular weights of 51.6, 24.0 and 13.3 kDa. The CAV genome moreover contains one evident promoter/enhancer region and only one polyadenylation signal. Transcription of the replicative DNA intermediary produces a polyadenylated polycistronic RNA molecule of approximately 2100 nucleotides (Noteborn et al., 1992b).
Day-old chicks are most susceptible to CAV infections. In these animals lethargy, anorexia and anemia are observed fro

REFERENCES:
patent: 5554525 (1996-09-01), Sondermeijer et al.
Meehan, B.M. et al. Arch. Virol., vol. 124, pp. 301-319, 1992.
Chandratilleke, D. et al. Avian Diseases, vol. 35, pp. 854-862, 1991.
Gelderbloom et al., (1989) Archives of Virol. 109:115-120.
Jeurissen et al., (1992) J. Virol. 66:7383-7388.
Noteborn et al., (1991) J. Virol. 65:3131-3139.
Noteborn et al., (1992) Avian Pathology 21:107-118.
Noteborn et al., (1992) Gene 118:267-271.
Noteborn et al., (1993) In: Vaccines 93, CSHL Press. Cold Spring Harbor, USA:299-304.
Ramakrishnan et al., (1993) Nature 362:217-223.
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