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Multi-epitope vaccines: a promising strategy against tumors and viral infections

Cellular & Molecular Immunology volume 15, pages 182–184 (2018)Cite this article

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Compared to classical vaccines and single-epitope vaccines, multi-epitope vaccines have unique design concepts4, 5, 6, 7, 8, 9, 10, 11 with the following properties: (I) they consist of multiple MHC-restricted epitopes that can be recognized by TCRs of multiple clones from various T-cell subsets; (II) they consist of CTL, Th and B-cell epitopes that can induce strong cellular and humoral immune responses simultaneously; (III) they consist of multiple epitopes from different tumor or virus antigens that can expand the spectra of targeted tumors or viruses; (IV) they introduce some components with adjuvant capacity that can enhance the immunogenicity and long-lasting immune responses; and (V) they reduce unwanted components that can trigger either pathological immune responses or adverse effects. Well-designed multi-epitope vaccines with such advantages should become powerful prophylactic and therapeutic agents against tumors and viral infections.

Current problems in the field of multi-epitope vaccine design and development include the selection of appropriate candidate antigens and their immunodominant epitopes and the development of an effective delivery system. Development of a successful multi-epitope vaccine first depends on the selection of appropriate candidate antigens and their immunodominant epitopes. The prediction of appropriate antigenic epitopes of a target protein by immunoinformatic methods is extremely important for designing a multi-epitope vaccine.12, 13 In our laboratory, we always use immunoinformatic tools to predict and screen the immunogenic T- and B-cell epitopes of the target antigens, then design peptides rich in epitopes or overlapping epitopes.7, 8, 11, 14, 15 For the prediction of B-cell epitopes, multiple alignments of the target antigen are initially carried out using software from the European Bioinformatics Institute website (http://www.ebi.ac.uk/Tools/clustalw2). Then, the structure, hydrophilicity and flexibility, and transmembrane domains of the target antigen are predicted and analyzed by methods including GOR,16 Hoop and Woods17 and artificial neural network (http://strucbio.biologie.uni-konstanz.de). Antigenic propensity value is further evaluated using the Kolaskar and Tongaonkar approach (http://bio.dfci.harvard.edu/Tools/antigenic.pl). Finally, the B-cell-dominant epitope is determined by comprehensive analysis and comparison, and T-cell epitopes including MHC-I restriction CTL and MHC-restriction Th epitopes are predicted using the SYFPEITHI network database (http://www.syfpeithi.de/Scripts/MHCServer.dll/EpitopePrediction.htm). All the above-mentioned programs are provided on the EXPASY server (http://www.expasy.org/tools). Recently, we have developed a multi-epitope vaccine, named EBV LMP2m, which encodes multiple CTL, Th and B epitopes from the EBV LMP2 gene.11 Expression of the recombinant multi-epitope protein from the constructed multi-epitope vaccine gene was optimized to maximize its production in E. coli. The specific CTL and Th cell reactions and B-cell activation (serum-specific IgG and mucosal IgA antibodies) were analyzed in BALB/c mice immunized with the multi-epitope vaccine. The multi-epitope-specific serum antibodies in patients with EBV-related tumors (nasopharyngeal carcinoma) or EBV infection were analyzed using ELISA and western blotting. All the analyses demonstrated that the multi-epitope vaccine EBV LMP2m had a very high immunogenicity. Therefore, EBV LMP2m could be considered as a potential vaccine candidate and diagnostic agent.

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  1. Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Wenzhou, 325035, China

    Lifang Zhang

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Zhang, L. Multi-epitope vaccines: a promising strategy against tumors and viral infections. Cell Mol Immunol 15, 182–184 (2018). https://doi.org/10.1038/cmi.2017.92

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