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摘要
Background: Human herpes simplex virus (HSV) 1 and 2 causes oral, ocular, or genital infections, which remains a significant health problem worldwide. HSV-1 and -2 infections in humans range from localized skin infections of the oral, ocular, and genital regions to severe and often disseminated infections in immunocompromised hosts. Epitope based vaccination is a promising mean to achieve protective immunity and to avoid infections with Human herpes simplex virus type 2 (HSV-2). Methods: The twelve selected epitopes, six B cell epitopes from different glycoprotein of HSV-2 (amino acid residues 466-473 (EQDRKPRN) from envelope glycoprotein B, 216-223 (GRTDRPSA) from C, 6-18 (DPSLKMADPNRFR) from D, 483-491 (DPPERPDSP) from E, 572-579 (EPPDDDDS) from G and 286-295 (CRRRYRRPRG) from I glycoprotein of HSV-2), four CD4(+) T cell epitopes (amino acid residues 21-28 (NLPVLDQL) from D, 162-177 (KDVTVSQVWFGHRYSQ) from B, 205-224 (KAYQQGVTVDSIGMLPRFIP) from D and 245-259 (KPPYTSTLLPPELSD) from D) and two CD8(+) T cell epitopes (amino acid residues 10-20 (KMADPNRFRGK) from D and 268-276 (ALLEDPAGT) from D), are responsible for the elicitation of the neutralizing antibodies and cytotoxic T lymphocytes (CTLs) that impart protective immunity to the host. In this study, all above epitopes were inserted into the extracellular fragment (amino acid residues 1-290) of HSV-2 glycoprotein D to construct multi-epitope assembly peptides (MEAPs) by replacing some non-epitope amino acid sequences. The epitope independency of the MEAPs was predicted by three-dimensional software algorithms. The gene of the selected MEAP was expressed in E.coli BL21 (DE3), and its protective efficacy against HSV-2 infection was assessed in BALB/c mice. Results: The MEAP, with each inserted epitopes independently displayed on the molecule surface, was selected as candidate proteins. The results showed that the MEAP was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses. Conclusions: The MEAP provided complete protection against infection with HSV-2 in mice, which indicates that it might be a potential candidate vaccine against HSV-2.
