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EBV LMP2A武装的改良安卡拉-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作用

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

作者信息

Sun Liying, Liu Chao, Peng Junping

机构信息

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.

State Key Laboratory of Stress Biology, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.

出版信息

Pharmaceutics. 2025 Jan 3;17(1):52. doi: 10.3390/pharmaceutics17010052.

DOI:10.3390/pharmaceutics17010052
PMID:39861700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11768126/
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 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.

摘要

背景

爱泼斯坦-巴尔病毒（EBV）与一系列人类恶性肿瘤密切相关，EBV潜伏膜蛋白2A（LMP2A）成为鼻咽癌（NPC）免疫治疗策略的潜在靶抗原。

方法

改良安卡拉痘苗病毒（MVA）因其出色的安全性和高效的重组基因表达而广泛用于载体疫苗研究。在此，我们构建了一种新型MVA-LMP2A重组病毒，并研究了其特异性免疫反应诱导和溶瘤作用。

结果

2×10 PFU的免疫剂量诱导了最高的特异性免疫反应，四剂后加强注射不再增加。末次免疫后三周，特异性免疫反应达到峰值。MVA-LMP2A疫苗诱导的LMP2A特异性细胞毒性T淋巴细胞（CTL）对靶细胞表现出显著疗效，并有效抑制肿瘤生长。

结论

因此，MVA-LMP2A重组病毒有效地诱导了强烈的LMP2A特异性细胞和体液免疫反应以及抗肿瘤活性。这项工作为开发NPC候选疫苗提供了一种有前景的治疗策略，也为治疗EBV LMP2相关恶性肿瘤提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/e830a0853454/pharmaceutics-17-00052-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/dd4383854910/pharmaceutics-17-00052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/560bad7a9dbe/pharmaceutics-17-00052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/11983a741e49/pharmaceutics-17-00052-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/e830a0853454/pharmaceutics-17-00052-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/4235b0187244/pharmaceutics-17-00052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/d3653ecec2d4/pharmaceutics-17-00052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/41c49d110dd3/pharmaceutics-17-00052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/cc7ae93424f9/pharmaceutics-17-00052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/dd4383854910/pharmaceutics-17-00052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/560bad7a9dbe/pharmaceutics-17-00052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/11983a741e49/pharmaceutics-17-00052-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/683d/11768126/e830a0853454/pharmaceutics-17-00052-g008.jpg

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