Identification of B- and T-cell epitopes from glycoprotein B of herpes simplex virus 2 and evaluation of their immunogenicity and protection efficacy

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• 作者：Kun Liu^a ; Deyu Jiang^a ; ^b ; Liangyan Zhang^a ; Zhidong Yao^a ; Zhongwei Chen^a ; Sanke Yu^b ; Xiliang Wang^a ; ^{xiliangw@126.com}
• 关键词：Herpes simplex virus ; gB protein ; B-cell epitopes ; Neutralizing antibodies ; T-cell epitopes ; Cytotoxic CD8+ T cells
• 刊名：Vaccine
• 出版年：2012
• 期刊代码：89_0264410x
• 类别：imm
• 出版时间：19 April, 2012
• 卷：30
• 期：19
• 页码：3034-3041
• 文件大小：1021 K

摘要

Herpes simplex virus (HSV) infection is a major health concern worldwide. Evidence obtained from animals and humans indicates that B- and T-cell responses contribute to protective immunity against herpes virus infection. Glycoprotein B is a transmembrane envelope component of HSV-1 and HSV-2, which plays an important role in virion morphogenesis and penetration into host cells, and can induce neutralizing antibodies and protective T-cell response when it is used to immunize humans and animals. However, little is known about gB epitopes that are involved in B- and T-cell activities in vitro and in vivo. Thus, the HSV-2 gB sequence was screened using B- and T-cell epitope prediction systems, and the B-cell regions and the HLA-A*0201-restricted epitopes were identified. These B-cell epitopes elicited high IgG antibody titers in Balb/C mice, with a predominantly IgG1 subclass distribution, which indicated a Th2 bias. Specific IgGs induced by these two epitopes were evaluated as the neutralizing antibodies for virus neutralization. The predicted T-cell epitopes stabilized the HLA-A*0201 molecules on T₂ cells, and stimulate interferon-纬-secreting and cytotoxic CD8⁺ T cells. Immunization with the predicted peptides reduced virus shedding and protected against lethal viral challenge in mice. The functional epitopes described herein, both B- and T-cell epitopes, are potentially implicated in vaccine development.