CTL epitopes from EBV

An epitope-free technology, applied in the field of subunit vaccines and nucleic acid vaccines, can solve problems such as blocking CTL

Inactive Publication Date: 2000-10-11
COUNCIL OF THE QUEENSLAND INST OF MEDICAL RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Immunosuppression blocks these specific CTLs, leading to the expansion of EBV-infected B cells and the clinical problems associated with PTLD

Method used

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  • CTL epitopes from EBV
  • CTL epitopes from EBV
  • CTL epitopes from EBV

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0071] Materials and methods

[0072] Cell line establishment and maintenance

[0073] LCLs were established from seropositive donors by heterologous viral transformation of peripheral B cells with B95.8 (type 1) or Ag876 (type 2) virus isolates. Furthermore, LCLs transformed with the B95.8 isolate expressing different HLA A2 supertypes (12th Histocompatibility Symposium cell series; EACC) were also used in this study. The peptide transporter (TAP) negative BxT hybrid cell line 174xCEM.T2 (denoted T2) (22) was used for peptide stability assays. All cell lines were routinely cultured in RPMI 1640 containing 2 mM glutamate, 100 IU / ml penicillin, 100 μg / ml streptomycin plus 10% fetal calf serum (FCS) (growth medium). Long-term cultures of EBV-negative normal B-cell blasts were established using the CD40 system (represented by CD40 B cells) as previously described (12).

[0074] The Burkitt lymphoma (BL) cell lines BJAB.gptl, BJAB.MTLM6, MUTUcl.59 and MUTUcl.216 were used in th...

Embodiment 2

[0118] Materials and methods

[0119] Patients with infectious mononucleosis (IM)

[0120] IM patients clinically identified as positive for metachromatic antibodies were bled 5-10 days after the onset of illness. In two cases, these patients were HLA-typed for the HLA A2 allele with microcytotoxic serotyping and genotyping 24-36 months after the end of the second phase of symptoms. Three patients (SB, LP, and MG) were identified as HLAA2-positive, which was subsequently confirmed by FACS analysis with an HLA A2-specific monoclonal antibody (ATCC).

[0121] Cell line establishment and maintenance

[0122] Transformation of peripheral B cells with type 1 (B95.5) or type 2 (Ag876) EBV isolates via exogenous virus, EBV-transformed lymphoblastoid cell lines (LCLs) from IM and healthy EBV seropositive donors Cell plates were established (16) and routinely maintained in RPMI 1640 (growth medium) containing 2 mM glutamate, 100 IU / ml penicillin and 100 μg / ml streptomycin plus 10% f...

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Abstract

The present invention provides cytotoxic Epstein-Barr virus (EBV) T-cell epitopes derived from EBV structural antigens. Preferred epitopes include YLLEMLWRL (SEQ ID NO:1), YFLEILWGL (SEQ ID NO:32), YLLEILWRL (SEQ ID NO:33), YLQQNWWTL (SEQ ID NO:6), LLLALLFWL (SEQ ID NO:2), LLVDLLWLL (SEQ ID NO:3), LLLIALWNL (SEQ ID NO:4), WLLLFLAIL (SEQ ID NO:5), TLLVDLLWL (SEQ ID NO:7), LLWLLLFLA (SEQ ID NO:8), ILLIIALYL (SEQ ID NO:9), VLFIFGCLL (SEQ ID NO:10), RLGATIWQL (SEQ ID NO:11), ILYFIAFAL (SEQ ID NO:15), SLVIVTTFV (SEQ ID NO:17), LMIIPLINV (SEQ ID NO:20), TLFIGSHVV (SEQ ID NO:24), LIPETVPYI (SEQ ID NO:26), VLQWASLAV (SEQ ID NO:27) and QLTPHTKAV (SEQ ID NO:29). The present invention also provides methods of treating or preventing EBV infection in subjects which involve administration of EBV cytotoxic T-cell epitopes.

Description

field of invention [0001] The present invention relates to methods of treating or preventing EBV infection. The present invention also relates to cytotoxic T cell (CTL) epitopes in Epstein-Barr virus (EBV) structural antigens and latent antigens, and subunit vaccines and nucleic acid vaccines comprising these epitopes. Background of the invention [0002] It is now well established that long-term protection from persistent viral infection requires the development of virus-specific memory T cells that recognize viral antigens associated with class I or class II MHC molecules. Because immunization with viral whole proteins fails to elicit efficient CTL responses, there has been interest in designing vaccines based on specific epitope sequences, especially for oncogenic viruses, since genes introduced into individual viruses in recombinant vectors have the initial oncogenic potential. process potential. Two main approaches are currently considered to design effective vaccines...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7088A61K39/00A61K39/245A61K39/295A61K48/00C12N15/09A61P31/12A61P35/00A61P43/00C07K7/06C07K14/05C07K16/08
CPCC12N2710/16622C12N2710/16222A61K39/00C07K14/005A61P31/12A61P31/20A61P35/00A61P43/00Y02A50/30
Inventor 斯科特·伦顿·伯罗斯拉吉夫·康纳马丁纳·艾利森·谢里特
Owner COUNCIL OF THE QUEENSLAND INST OF MEDICAL RES
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