Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1997-01-27
1999-02-09
Feisee, Lila
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 13, 514613, 530328, 530326, 530327, A61K 3800, C07K 500
Patent
active
058694536
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to cytotoxic T-cell (CTL) epitopes within Epstein-Barr virus. The present invention also relates to the use of the epitopes in subunit vaccines.
BACKGROUND OF THE INVENTION
Epstein-Barr virus (EBV) is a herpes virus that infects approximately 80% of individuals in Western societies. Following primary infection, a life long latent EBV infection of B cells is established. When primary infection is delayed until adolescence, which occurs in 10-20% of individuals in Western societies, there is an approximately 50% chance of developing infectious mononucleosis.
EBV has the very useful property of being able to "immortalise" or transform human B cells. These transformed B cells (referred to as LCLs) have the potential for essentially unlimited growth in the laboratory. There are two methods by which these LCLs can be established. Firstly, they may be established by the use of a common strain of EBV, referred to as B95.8. The LCL that is established is infected with this strain of virus. Secondly, LCLs may be generated using the latently infected B cells, present in all EBV immune individuals as a source of transforming virus. In this case, the LCL that emerges is transformed with the strain of EBV naturally present in any given EBV immune individual (referred to as spontaneous LCL).
There are two EBV types, A and B. The A type appears to predominate in the majority of lymphoid infections of healthy seropositive individuals. In such individuals, latently infected B cells appear to be controlled by CD8+ cytotoxic T cells (CTL) specific for the latent antigens, which include the EBV nuclear antigens (EBNAs) 2-6 and the latent membrane antigens (LMP) 1-3 (Moss, D. J. et al. 1992). Recent developments suggests that CD4+ CTL may also play a part in controlling this infection. These CTL are known to recognise short peptide epitopes derived from antigenic determinants in association with MHC class I molecules on the surface of an appropriate antigen presenting cell. LCLs displaying HLA class I and II alleles and presenting epitopes within EBV latent antigens are frequently used as a target cell for defining the specificity of CTL clones.
As whole virus or recombinant vaccines based on full length latent proteins are considered potentially oncogenic, an EBV vaccine based on CTL epitopes derived from the latent antigens is currently being developed (Moss, D. J. et al 1993). Khanna et al, (1992) have previously described several CTL epitopes.
SUMMARY OF THE INVENTION
In a first aspect the present invention consists in cytotoxic T-cell epitopes from Epstein-Barr virus.
More specifically, there is provided twelve cytotoxic T-cell epitopes from the Epstein-Barr virus latent antigens having the amino acid sequences QAKWRLQTL SEQ ID NO:11, RYSIFFDY SEQ ID NO:13, HLAAQGMAY SEQ ID NO:5, YPLHEQHGM SEQ ID NO:23 (YPLHKOHGM SEQ ID NO:25, YRLHEOHGM SEQ ID NO:26, YPLHEORGM SEQ ID NO:24) SVRDRLARL SEQ ID NO:15, AVLLHEESM SEQ ID NO:1 (TVLLHEESM SEQ ID NO:19 and TALLHEESM SEQ ID NO:16), VSFIEFVGW SEQ ID NO:22, FRKAQIQGL SEQ ID NO:3, PYLFWLAAI SEQ ID NO:10, TVFYNIPPMPL SEQ ID NO:18, PGDQLPGFSDGRACPV SEQ ID NO:9 and VEITPYKPTW SEQ ID NO:20. In addition, the underlined amino acid sequences in brackets are variants of the aforementioned sequence and have been sequenced from geographically different isolates of Epstein-Barr virus. It has not as yet been established whether these variants are CTL epitopes.
In a second aspect the present invention consists in a composition for use in inducing CTL's in a subject, the composition comprising at least one cytotoxic Epstein-Barr virus T-cell epitope according to the first aspect of the present invention in admixture with at least one pharmaceutical acceptable adjuvant, carrier, diluent or excipient.
In a third aspect the present invention consists in a method of preparing a composition for use in inducing CTL's in a subject, the method comprising admixing at least one cytotoxic Epstein-Barr virus T-cell according to the first aspect of the p
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Burrows Jacqueline Margaret
Burrows Scott Renton
Kerr Beverley Mavis
Khanna Rajiv
Moss Denis James
Bansal Geetha P.
Feisee Lila
The Council of the Queensland Institute of Medical Research
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