The Epstein-Barr Virus Lytic Protein BZLF1 as a Candidate Target Antigen for Vaccine Development.
The Epstein-Barr Virus Lytic Protein BZLF1 as a Candidate Target Antigen for Vaccine Development.
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DOI：
10.1158/2326-6066.cir-14-0242
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发表时间：
2015-07
影响因子：
10.1
通讯作者：
Baiocchi RA
中科院分区：
文献类型：
--
作者：
Hartlage AS;Liu T;Patton JT;Garman SL;Zhang X;Kurt H;Lozanski G;Lustberg ME;Caligiuri MA;Baiocchi RA
EB病毒（EBV）是一种与广谱疾病相关的致癌γ-疱疹病毒。虽然大多数有免疫能力的个体可以有效地对EBV产生有效的适应性免疫应答，但免疫功能低下的个体处于发展威胁生命的疾病如霍奇金淋巴瘤和移植后淋巴组织增生性疾病（PTLD）的严重风险中。鉴于在高危人群中与EBV感染相关的显著发病率，需要开发恢复或增强EBV特异性免疫应答的疫苗策略。在这里，我们确定EBV立即早期蛋白BZLF 1作为疫苗开发的潜在靶抗原。PTLD患者的原发性肿瘤和EBV驱动的淋巴增生性疾病（EBV-LPD）的嵌合人-鼠模型表达BZLF 1蛋白。用重组BZLF 1脉冲人树突状细胞（DC），然后与自体单核细胞孵育，导致BZLF 1特异性CD 8（+）T细胞在体外扩增，并在体内引发BZLF 1特异性T细胞应答。此外，用BZLF 1转导的DC接种hu-PBL-SCID小鼠诱导特异性细胞免疫，并显著延长致命性EBV-LPD的存活。这些发现确定BZLF 1作为EBV免疫监视的候选靶蛋白，并为在疫苗策略中考虑BZLF 1以增强原发性和回忆性免疫应答并潜在地预防EBV相关疾病提供了理论基础。
The Epstein-Barr virus (EBV) is an oncogenic, γ-herpesvirus associated with a broad spectrum of disease. While most immune-competent individuals can effectivley develop efficient adaptive immune responses to EBV, immunocompromised individuals are at serious risk for developing life threatening diseases such as Hodgkin’s lymphoma and post-transplant lymphoproliferative disorder (PTLD). Given the significant morbidity associated with EBV infection in high-risk populations, there is a need to develop vaccine strategies that restore or enhance EBV-specific immune responses. Here, we identify the EBV immediate-early protein BZLF1 as a potential target antigen for vaccine development. Primary tumors from patients with PTLD and a chimeric human-murine model of EBV-driven lymphoproliferative disorder (EBV-LPD) express BZLF1 protein. Pulsing human dendritic cells (DC) with recombinant BZLF1 followed by incubation with autologous mononuclear cells led to expansion of BZLF1-specific CD8(+) T cells in vitro and primed BZLF1-specific T-cell responses in vivo. In addition, vaccination of hu-PBL-SCID mice with BZLF1-transduced DCs induced specific cellular immunity and significantly prolonged survival from fatal EBV-LPD. These findings identify BZLF1 as a candidate target protein in the immunosurveillance of EBV and provide rationale for considering BZLF1 in vaccine strategies to enhance primary and recall immune responses and potentially prevent EBV-associated diseases.