TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice.

IF 8.4 2区 医学 Q1 IMMUNOLOGY Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-10-13 DOI:10.1080/22221751.2024.2412640
Xinyu Zhang, Yanhong Chen, Shuhui Wang, Ling Zhong, Zheng Xiang, Xiao Zhang, Shanshan Zhang, Xiang Zhou, Wanlin Zhang, Yan Zhou, Qiuting Zhang, Jingtong Liang, Yanran Luo, Yufei Wang, Ling Chen, Xiaoping Ye, Qisheng Feng, Mu-Sheng Zeng, Ying Liu, Yi-Xin Zeng, Yiming Shao, Miao Xu
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Abstract

Epstein-Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

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基于天坛疫苗病毒的 EBV 疫苗同时针对潜伏抗原和溶解抗原,可在人源化小鼠体内激发针对致命性 EBV 挑战的强效免疫力。
摘要天疱疮病毒(EBV)感染与多种上皮癌和淋巴瘤有关。目前,开发预防性 EBV 疫苗的工作主要集中在诱导中和抗体上。然而,鉴于 EBV 感染在原发感染后会终身持续存在,因此理想的疫苗应该针对 EBV 生命周期的多个阶段引起体液免疫和细胞免疫反应。本研究使用 DNA 载体和天坛疫苗病毒表达 EBV 的关键抗原,包括 BZLF1、EBNA1、EBNA3B 和 gH/gL,以产生多抗原疫苗。通过激活 BZLF1、EBNA1 和 EBNA3B 特异性 T 细胞,表达所有四种抗原的多抗原疫苗和表达 BZLF1、EBNA1 和 EBNA3B 的多抗原疫苗显示出了相当的保护效果,分别 100% 和 80% 的人源化小鼠免于 EBV 诱导的致命 B 细胞淋巴瘤。与针对单一潜伏 EBNA1 或 EBNA3B 的疫苗相比,表达溶菌蛋白 BZLF1 的疫苗能激发更强的 T 细胞反应,并提供更优越的保护。在我们的人源化小鼠模型中,仅表达 gH/gL 的疫苗没有表现出 T 细胞保护作用。我们的研究表明,针对 EBV 生命周期的潜伏期和溶解期诱导强效细胞应答的 EBV 疫苗具有预防 EBV 诱导的 B 细胞淋巴瘤的潜力。
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来源期刊
Emerging Microbes & Infections
Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY
CiteScore
26.20
自引率
2.30%
发文量
276
审稿时长
20 weeks
期刊介绍: Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.
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