Role of Mucosal Immunity in Vaccine Protection

粘膜免疫在疫苗保护中的作用

• 批准号: 7052873
• 负责人: KRISTINA E HOWARD
• 金额: $ 11.39万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052873
• 关键词: AIDS vaccines; HIV envelope protein; HIV infections; Listeria; T lymphocyte; biotechnology; cats; cell death; disease /disorder model; enzyme linked immunosorbent assay; feline immunodeficiency virus; gag protein; immunization; immunologic receptors; interferon gamma; mucosal immunity; oral administration; receptor expression; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): The intermediate goal of the candidate, Kristina E. Howard, DVM, is to complete a mentored training program in retrovirus pathogenesis research, culminating in the PhD degree and providing the opportunity for continued postdoctoral study. Dr. Howard's long-term goal is to become a principal investigator employing animal models to investigate the mucosal immune pathogenesis of infectious diseases. The research training program will be conducted under the guidance of Dr. Gregg A. Dean and Dr. Wayne Tompkins, at North Carolina State University. The FlV research group, of which the co-sponsors are part, has a strong record of extramural funding and scientist training. The candidate's plan emphasizes laboratory training in the current molecular techniques and immunological research methods applied to an animal model of AIDS. This proposal employs the feline immunodeficiency virus (FIV) animal model in the testing of a novel oral vaccine strategy utilizing recombinant Listeria monocytogenes to express FIV proteins. The FIV/cat model is a well-established model of lentiviral immunodeficiency in a natural host that is characterized by the ability to initiate transmucosal infection utilizing either cell-associated or cell-free inoculum. Using a recombinant L. monocytogenes, we have recently shown that a single oral vaccination provided protection against vaginal FIV challenge. This proposal will characterize mucosal immunity conferred by this vaccine and assess potential mechanisms of protection. In the first aim we will assess mucosal and systemic immune responses following vaccination to better understand the specific responses induced by the vaccine. Aim 2 will assess the ability of the oral vaccine to protect against homologous versus heterologous mucosal FIV challenge and determine what specific humoral and cell-mediated immune responses may correlate with protection. Aim 3 addresses potential mechanisms by which this vaccine may protect the host from FIV infection. The results of these studies will provide establish whether or not this vaccine can protect against diverse FIV challenge, will identify mucosal immune responses that may be responsible for protection, and may identify additional immune system targets for enhanced vaccine development and therapeutic intervention.

描述（由申请人提供）：候选人的中间目标，克里斯蒂娜E。霍华德，DVM，是完成在逆转录病毒发病机制研究的指导培训计划，最终在博士学位，并提供继续博士后研究的机会。霍华德博士的长期目标是成为一名主要研究者，采用动物模型研究感染性疾病的粘膜免疫发病机制。研究培训计划将在Gregg A.博士的指导下进行。北卡罗来纳州州立大学院长和韦恩·汤普金斯博士。FLV研究小组，其中共同赞助商的一部分，有一个强大的记录校外资金和科学家培训。候选人的计划强调当前分子技术和应用于艾滋病动物模型的免疫学研究方法的实验室培训。 该建议采用猫免疫缺陷病毒（FIV）动物模型，利用重组单核细胞增生李斯特菌表达FIV蛋白的新型口服疫苗策略的测试。FIV/猫模型是天然宿主中慢病毒免疫缺陷的成熟模型，其特征在于能够利用细胞相关或无细胞接种物启动经粘膜感染。利用重组L.在单核细胞增多症中，我们最近表明单次口服疫苗接种提供了针对阴道FIV攻击的保护。该提案将描述该疫苗赋予的粘膜免疫力，并评估潜在的保护机制。在第一个目标中，我们将评估疫苗接种后的粘膜和全身免疫应答，以更好地了解疫苗诱导的特异性应答。目的2将评估口服疫苗对同源与异源粘膜FIV攻击的保护能力，并确定哪些特异性体液和细胞介导的免疫应答可能与保护相关。目的3阐述了该疫苗保护宿主免受FIV感染的潜在机制。这些研究的结果将确定该疫苗是否可以针对不同的FIV攻击提供保护，将鉴定可能负责保护的粘膜免疫应答，并可能鉴定用于增强疫苗开发和治疗干预的其他免疫系统靶标。