NOVEL DELIVERY SYSTEM FOR A HERPESVIRUS DNA VACCINE

疱疹病毒 DNA 疫苗的新型递送系统

• 批准号: 2897191
• 负责人: NANCY J BIGLEY
• 金额: $ 3.6万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2897191
• 关键词: Herpesviridae vaccine; T cell receptor; active immunization; cytotoxic T lymphocyte; drug delivery systems; flow cytometry; gene expression; helper T lymphocyte; herpes simplex virus 1; histocompatibility antigens; immunocytochemistry; injection /infusion; laboratory mouse; lysine; monoclonal antibody; plasmids; polymerase chain reaction; proteoglycan; tissue /cell culture; vector vaccine; virus DNA; virus cytopathogenic effect; virus infection mechanism

Most adults harbor herpes simplex virus type I(HSV-1) but only some suffer periodic episodes of painful fever blisters. T cells limit viral pathogenesis by inducing a nonpermissive state in ganglion cells, where the virus lies latent. Cytotoxic T lymphocytes (CTL), especially CD4+ CTL, are critical in resistance against recurrent herpes lesions. Viral glycoproteins (gP), expressed early in HSV infection are CTL targets and have been used as therapeutic vaccines with some success. Although living vaccines are usually needed to stimulate effective CTL responses, naked DNA vaccines encoding HSV gP stimulate CTL and antibody responses experimentally. The hypothesis of this study is that a DNA vaccine encoding HSV-1 glycoprotin D (gD), protected from nuclease activity and targeted to cells bearing receptors for asialoorosomucoid (ASOR), can stimulate specific cellular immunity to herpes simplex virus in mice. The novelty of this strategy is that ligands, such as poly-L-lysine-ASOR (ASOR-L), protect the DNA from nucleases while directing it to cells bearing receptors for the ligand, features lacking in naked HSV gP DNA vaccines. To test the hypothesis, gD DNA either complexed to ASOR-L or naked will be injected into BALB/c and C3H mice by 4 different routes [intravenous (iv), intraperitoneal (ip), intramuscular (im), and oral (po)]. At 2 weeks after injection of 10 mug doses of DNA, splenic T cells will be examined for CTL activity against histocompatible target cells expressing gD. Since hepatocytes, macrophages and enterocytes bear receptors for ASOR, higher levels of gD-specific CTL activity will more likely develop in mice receiving gD-ASOR by iv, ip and po routes. Conditions for stimulating optimal HSV CTL responses will be defined by this study. The practical application of this novel approach is a therapy for alleviating recurrences of painful herpes lesions in humans.

大多数成年人携带I型单纯疱疹病毒（HSV-1），但只有一部分

项目成果

Murine response to DNA encoding herpes simplex virus type-1 glycoprotein D targeted to the liver.

• DOI: 10.1016/s0264-410x(99)00438-7
• 发表时间: 2000-02
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: J. Rogers;B. Hull;P. Fink;H. Chiou;N. J. Bigley

Targeted delivery of DNA encoding herpes simplex virus type-1 glycoprotein D enhances the cellular response to primary viral challenge.

编码单纯疱疹病毒 1 型糖蛋白 D 的 DNA 的靶向递送可增强细胞对初次病毒攻击的反应。

• DOI: 10.1007/s004030000181
• 发表时间: 2000
• 期刊: Archives of dermatological research
• 影响因子: 3
• 作者: Rogers,JV;Bigley,NJ;Chiou,HC;Hull,BE
• 通讯作者: Hull,BE