Specific Immune Responses and Oncolytic Effects Induced by EBV LMP2A-Armed Modified Ankara-Vaccinia Virus Vectored Vaccines in Nasopharyngeal Cancer

EBV LMP2A 武装的改良型安卡拉痘苗病毒载体疫苗在鼻咽癌中诱导的特异性免疫反应和溶瘤效应

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Abstract

BACKGROUND: The Epstein-Barr virus (EBV) is intricately linked to a range of human malignancies, with EBV latent membrane protein 2A (LMP2A) emerging as a potential target antigen for immunotherapeutic strategies in the treatment of nasopharyngeal carcinoma (NPC). METHODS: The modified vaccinia virus Ankara (MVA) is universally used in vector vaccine research because of its excellent safety profile and highly efficient recombinant gene expression. Here, we constructed a novel MVA-LMP2A recombinant virus and investigated its specific immune response induction and oncolytic effect. RESULTS: An immunization dose of 2 × 10(7) PFU induced the highest specific immune response, which was no longer increased by boost injections after four doses. Three weeks post-final immunization, the specific immune response reached its peak. The MVA-LMP2A vaccine-induced LMP2A-specific cytotoxic T lymphocytes (CTLs), which exhibited substantial efficacy against target cells and effectively inhibited tumor growth. CONCLUSIONS: Thus, the MVA-LMP2A recombinant virus effectively induces strong LMP2A-specific cellular and humoral immune responses and anti-tumor activity. This work provides a promising therapeutic strategy for developing NPC candidate vaccines, as well as a reference for the treatment of EBV LMP2-associated malignancies.

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