A LEAPS™ heteroconjugate vaccine containing a T cell epitope from HSV-1 glycoprotein D elicits Th1 responses and protection

A LEAPS™ heteroconjugate vaccine containing a T cell epitope from HSV-1 glycoprotein D elicits Th1 responses and protection
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DOI:
10.1016/s0264-410x(03)00429-8
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发表时间:
2003-10-01
期刊:
影响因子:
5.5
通讯作者:
Rosenthal, KS
Rosenthal, KS
中科院分区:
医学3区
文献类型:
--
作者:
Goel, N;Rong, Q;Rosenthal, KS

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L.E.A.P.S. (TM)由来自单纯疱疹病毒(HSV)糖蛋白D(gD(8-23))的T细胞表位与来自β-2-微球蛋白(aa 38 -50)的肽序列连接组成的异源缀合疫苗抗原(JgD)引起对致死性腹膜内(IP)攻击的保护,并在大多数情况下预防疾病体征,并限制疾病进展,对于在表皮擦伤-带状疱疹样传播小鼠感染模型中攻击的其余BALB/c小鼠。JgD在接种疫苗的小鼠中引起Th 1应答,如对HSV抗原的迟发型超敏反应(DTH)所示,并且gD和病毒体特异性抗体具有IgG 2a/IgG 1> 1。与其各自的对照小鼠相比,用JgD肽接种延迟了具有不同MHC背景的小鼠中疾病体征的发作,降低了疾病的严重程度并降低了死亡率。如单克隆抗体消融研究所示,CD 8细胞被证明对于启动对JgD的免疫应答和CD 4细胞以及干扰素γ(IFN-γ)对于在BALB/c小鼠中提供免疫保护是重要的。JgD和其他J-L. E. A. P. S(TM)疫苗抗原似乎引发T细胞以启动Th 1应答,该应答随后在病毒攻击时加强以产生保护。(C)2003爱思唯尔有限公司。保留所有权利。
The L.E.A.P.S.(TM) heteroconjugate vaccine antigen (JgD), composed of a T cell epitope from glycoprotein D (gD(8-23)) of herpes simplex virus (HSV) linked with a peptide sequence from beta-2-microglobulin (aa38-50), elicited protection against lethal intraperitoneal (IP) challenge and prevented disease signs in most, and limited disease progression, for the rest of BALB/c mice challenged in the epidermal abrasion-zosteriform spread mouse infection model. JgD elicited a Th1 response in vaccinated mice as indicated by delayed type hypersensitivity (DTH) responses to HSV antigen, and gD and virion specific antibodies with an IgG2a/IgG1 > 1. Vaccination with the JgD peptide delayed the onset of disease signs, reduced severity of the disease and reduced mortality rates in mice with different MHC backgrounds as compared to their respective control mice. CD8 cells were demonstrated as important for initiation of the immune response to JgD and CD4 cells and interferon gamma (IFN-gamma) for delivering immune protection in BALB/c mice, as indicated in monoclonal antibody ablation studies. JgD, and other J-L.E.A.P.S(TM) vaccine antigens, appear to prime T cells to initiate a Th1 response, which is subsequently boosted upon viral challenge to result in protection. (C) 2003 Elsevier Ltd. All rights reserved.