DEVELOPMENT OF ROTAVIRUS DNA VACCINES

轮状病毒 DNA 疫苗的开发

• 批准号: 6816623
• 负责人: JOHN E HERRMANN
• 金额: $ 23.08万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6816623
• 关键词: B lymphocyte; Rotavirus; T lymphocyte; antigen antibody reaction; cellular immunity; complementary DNA; disease /disorder model; enzyme linked immunosorbent assay; intramuscular injections; laboratory mouse; mucosal immunity; oral administration; rotavirus vaccines; swine; vaccine development; vector vaccine

DESCRIPTION: (Adapted from Applicant's Abstract) The goal of our studies is to develop and test rotavirus DNA vaccines in mice and gnotobiotic pigs that will provide the basis for development of human rotavirus DNA vaccines. Rotaviruses are the major cause of severe acute diarrhea in children, resulting in an estimated 870,000 deaths per year, and current vaccines have not been effective in developing countries where the need is the greatest. We have shown that protective immunity in mice was obtained by parenteral inoculation of DNA vaccines encoding rotavirus proteins and by oral administration of rotavirus DNA vaccines encapsulated in poly (lactide-co-glycolide) (PLG) microparticles. We will evaluate protection generated by DNA vaccines in mice and in gnotobiotic or rotavirus antibody-free conventional pigs, the only animal models that can be clinically infected with human rotaviruses. Immunization will be by oral administration or by intramuscular inoculation with VP2, VP4, VP6 and VP7 DNA vaccines. VP7 is the major neutralization antigen of the outer capsid and the VP7 (G) serotypes 1-4 are the basis of the live, attenuated rhesus-human reassortant tetravalent rotavirus vaccine. To test the possibility of preparing VP7 DNA vaccines derived from human and simian rotaviruses, we will prepare one VP7 DNA vaccine from simian SA-11 rotavirus (for testing against EDIM rotavirus in the mouse model; EDIM and SA-11 are both G serotype 3 viruses), and one VP7 DNA vaccine from human Wa rotavirus (G serotype 1) for testing against Wa rotavirus challenge in gnotobiotic pigs. Mucosal and systemic immune responses to DNA vaccines will be examined in an adult mouse model and in gnotobiotic pigs or rotavirus antibody-free conventional pigs. The antibodies and specific isotypes induced by each DNA vaccine will be examined for virus neutralizing activity and epitope specificity. Cell-mediated immune responses to be examined in the mouse model include cytotoxic T cell responses and specific T helper cell subsets induced. Studies in pigs will include quantitating lymphoproliferative (T cell) and antibody secreting cell (B cell) responses from mucosal and systemic tissues. The need for improved rotavirus vaccines is a continuing one. Immunization with DNA vaccines that express specific rotaviral proteins offers a new approach to vaccination against rotaviruses and may provide the next generation of rotavirus vaccines.

描述：（根据申请人的摘要改编）我们研究的目的是 在小鼠和gnotobiotic猪中开发和测试轮状病毒DNA疫苗 为开发人轮状病毒DNA疫苗的发展提供了基础。轮状病毒 是儿童严重急性腹泻的主要原因，导致 估计每年870,000人死亡，当前的疫苗尚未有效 在最大需求的发展中国家中。我们已经表明 通过肠胃外接种DNA获得了小鼠的保护性免疫力 编码轮状病毒蛋白和轮状病毒的疫苗 DNA疫苗封装在聚乳酸 - 糖醇）（PLG）微粒中。 我们将评估DNA疫苗在小鼠和中产生的保护 gnotobiotic或轮状病毒抗体无常规猪，唯一的动物 可以在临床上感染人轮状病毒的模型。免疫 将通过口服给药或通过VP2，VP4， VP6和VP7 DNA疫苗。 VP7是外部的主要中和抗原 CAPSID和VP7（G）血清型1-4是活，减弱的基础 恒河 - 人类可重新成本的四腔轮状病毒疫苗。测试可能性 为了制备从人和猿猴轮状病毒衍生的VP7 DNA疫苗，我们 将从Simian SA-11轮状病毒中制备一种VP7 DNA疫苗（用于测试 针对小鼠模型中的Edim轮状病毒； Edim和SA-11都是G血清型3 病毒），以及一种来自人WA轮状病毒（G血清型1）的VP7 DNA疫苗 针对gnotobiotic猪中的WA轮状病毒挑战的测试。粘膜和 将在成年小鼠中检查对DNA疫苗的全身免疫反应 模型和gnotobiotic猪或轮状病毒抗体的常规猪。这 将检查每种DNA疫苗诱导的抗体和特定的同种型 用于中和活性和表位特异性。细胞介导的免疫 在鼠标模型中检查的响应包括细胞毒性T细胞反应 和特定的T辅助细胞子集引起的。猪的研究将包括 定量淋巴增生性（T细胞）和抗体分泌细胞（B细胞） 粘膜和全身组织的反应。需要改善轮状病毒的需求 疫苗是一种持续的疫苗。用表达的DNA疫苗免疫 特定的轮状病毒蛋白提供了一种新的方法来疫苗接种 轮状病毒，可能会提供下一代轮状病毒疫苗。

项目成果

DNA vaccines against enteric infections.

• DOI: 10.1016/j.vaccine.2005.07.012
• 发表时间: 2006-05
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: J. Herrmann

Mucosal and systemic antibody responses and protection induced by a prime/boost rotavirus-DNA vaccine in a gnotobiotic pig model.

• DOI: 10.1016/j.vaccine.2005.03.009
• 发表时间: 2005-06
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Lijuan Yuan;M. Azevedo;Ana M. González;K. Jeong;T. Van Nguyen;P. Lewis;C. Iosef;J. Herrmann;L. Saif