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Chimerically fused antigen rich of overlapped epitopes from latent membrane protein 2 (LMP2) of Epstein–Barr virus as a potential vaccine and diagnostic agent

Cellular & Molecular Immunology volume 13, pages 492–501 (2016)Cite this article

Abstract

Epstein–Barr virus (EBV) is prevalent throughout the world and is associated with several malignant diseases in humans. Latent membrane protein 2 (LMP2) of EBV plays a crucial role in the pathogenesis of EBV-associated tumors; therefore, LMP2 has been considered to be a potential immunodiagnostic and immunotherapeutic target. A multi-epitope-based antigen is a promising option for therapeutic vaccines and diagnoses of such malignancies. In this study, we systematically screened cytotoxic T lymphocyte (CTL), helper T cell (Th) and B-cell epitopes within EBV-LMP2 using bioinformatics. Based on the screen, two peptides rich in overlapping epitopes of both T cells and B cells were selected to construct a plasmid containing the sequence for a chimeric multi-epitope protein referred to as EBV-LMP2m, which is composed of LMP2aa195∼232 and LMP2aa419∼436. The EBV-LMP2m protein was expressed in E. coli BL21 (DE3) after prokaryotic codon optimization. Inoculation of the purified chimeric antigen in BALB/c mice induced not only high levels of specific IgG in the serum and secretory IgA in the vaginal mucus but also a specific CTL response. By using purified EBV-LMP2m as an antigen, the presence of specific IgG in the serum specimens of 202 nasopharyngeal carcinoma (NPC) patients was effectively detected with 52.84% sensitivity and 95.40% specificity, which represents an improvement over the traditional detection method based on VCA-IgA (60.53% sensitivity and 76.86% specificity). The above results indicate that EBV-LMP2m may be used not only as a potential target antigen for EBV-associated tumors but also a diagnostic agent for NPC patients.

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Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (No: 81372447).

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Author notes

  1. Xiaoyun Lin and Shao Chen: Both Xiaoyun Lin and Shao Chen contributed equally to this work.

  2. Lifang Zhang, Wenzhou Medical University, Wenzhou 325035, China. E-mail: wenzhouzlf@126.com

Authors and Affiliations

  1. Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, China

    Xiaoyun Lin, Shao Chen, Xiangyang Xue, Lijun Lu, Shanli Zhu, Wenshu Li, Xiangmin Chen, Xiaozhi Zhong, Pengfei Jiang, Torsoo Sophia Sename & Lifang Zhang

  2. School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China

    Yi Zheng

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Lin, X., Chen, S., Xue, X. et al. Chimerically fused antigen rich of overlapped epitopes from latent membrane protein 2 (LMP2) of Epstein–Barr virus as a potential vaccine and diagnostic agent. Cell Mol Immunol 13, 492–501 (2016). https://doi.org/10.1038/cmi.2015.29

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