a RT-Europe Nonprofit Research Center , Mosonmagyaróvár , Hungary.
b Galenbio Ltd , Mosonmagyaróvár , Hungary.
Expert Rev Vaccines. 2018 Mar;17(3):239-248. doi: 10.1080/14760584.2018.1425620. Epub 2018 Feb 9.
Despite overwhelming experimental work, there are no licensed vaccines against the most frequent Alphaherpesviruses, namely herpes simplex virus 1 and 2 (HSV1 and 2) nor against the Epstein-Barr virus (EBV), a member of the subfamily Gammaherpesvirus.
Since the DNAs of both HSVs reside in the regional sensory ganglia in a latent state (i.e. as circularized episomal molecules), a corresponding vaccine might be useful for immunotherapy rather than for prevention of primary infection. Here we describe the design of a purified subunit vaccine as well as the preparation and efficacy of a recombinant fusion protein consisting of the gD ectodomain from our domestic attenuated HSV1 strain HSZP. The EBV vaccines considered so far, were destined for prevention of infectious mononucleosis (IM) or to prevent formation of EBV related tumors. To design the EBV peptide vaccine, at least 15 carefully selected immunogenic epitopes coming from 12 virus coded proteins were bound to synthetic micro-particle carriers along with a non-specific pathogen recognizing receptor (PRR) stimulating both the T as well as B lymphocytes.
The efficacy of a novel EBV peptide in the rabbit model was based on criteria such as antibody formation (EA-D detected by ELISA, early and capsid proteins tested by immunoblot), presence of LMP1 antigen and of viral DNA in peripheral white blood cells. Out of 19 peptide combinations used for vaccination, at least 6 showed a satisfactory protective effect.
尽管有大量的实验工作,但目前还没有针对最常见的α疱疹病毒(即单纯疱疹病毒 1 型和 2 型[HSV1 和 HSV2])或针对 EBV(EBV)的许可疫苗,EBV 是γ疱疹病毒亚科的一员。
由于两种 HSV 的 DNA 以潜伏状态存在于区域性感觉神经节中(即作为环状的附加体分子),因此相应的疫苗可能对免疫治疗有用,而不是预防原发性感染。在这里,我们描述了纯化亚单位疫苗的设计,以及由我们国内减毒 HSV1 株 HSZP 的 gD 外显子组成的重组融合蛋白的制备和功效。迄今为止,所考虑的 EBV 疫苗旨在预防传染性单核细胞增多症(IM)或预防 EBV 相关肿瘤的形成。为了设计 EBV 肽疫苗,至少有 15 个精心挑选的来自 12 种病毒编码蛋白的免疫原性表位与合成微颗粒载体结合,同时结合一种非特异性病原体识别受体(PRR),刺激 T 细胞和 B 细胞。
新型 EBV 肽在兔模型中的功效是基于以下标准:抗体形成(通过 ELISA 检测 EA-D,通过免疫印迹检测早期和衣壳蛋白)、外周白细胞中存在 LMP1 抗原和病毒 DNA。在用于接种的 19 种肽组合中,至少有 6 种表现出令人满意的保护作用。