INDUCTION OF PROTECTIVE IMMUNITY TO LISTERIA IN NEONATES

诱导新生儿对李斯特菌的保护性免疫

• 批准号: 6916032
• 负责人: Tobias R. Kollmann
• 金额: $ 8.95万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916032
• 关键词: Listeria; Listeria infections; active immunization; age difference; antigen presentation; bactericidal immunity; cellular immunity; congenital infection; cytotoxic T lymphocyte; developmental immunology; gene expression; helper T lymphocyte; immunogenetics; immunologic memory; laboratory mouse; leukocyte activation /transformation; mature animal; microorganism culture; newborn animals; nucleic acid sequence

DESCRIPTION (provided by applicant): Listeria monocytogenes (LM) is a major pathogen in the neonate. LM is also being developed as a vaccine vehicle for heterologous vaccines from HIV to tumors. Most of these vaccines will be given to infants. Yet hardly anything is known about the immune response to LM in the neonate or infant. This is all the more surprising, as LM infection is one of the best-studied models in immunology, and excellent tools have been generated that have allowed the dissection and targeted manipulation of adult murine hostmicrobe in vivo interactions with their impact on immunity. We believe that an analysis of the neonatal immune response to LM infection employing these newly available tools will yield important mechanistic insights into not only neonatal LM infection, but also into vaccine design. We hypothesize a) that primary effector and memory T cells providing protective immunity to LM infection can be generated in the neonate; b) that it is mainly a deficit in neonatal antigen presentation that results in the neonate's heightened susceptibility to primary LM infection; and c) that it is neonate-specific regulatory pathways that provide the mechanistic underpinnings for the failure of functional memory T cell generation in the neonate in response to LM infection or vaccination. To test these hypotheses, we will take the approach successfully employed in the study of adult LM infection and vaccination, and apply these tools to the neonate. Similar to the tremendous impact the study of LM infection had on knowledge about immunology of the adult mouse, we believe our studies will address and bring to light fundamental issues in neonatal immunology and vaccinology.

描述（由申请人提供）：单核细胞增生李斯特菌（LM）是新生儿中的主要病原体。 LM也被开发为从HIV到肿瘤的异源疫苗的疫苗媒介。这些疫苗中的大多数都会给婴儿。然而，关于新生儿或婴儿中对LM的免疫反应几乎没有任何了解。这是更令人惊讶的，因为LM感染是免疫学上最有研究的模型之一，并且已经产生了出色的工具，可以使成年鼠宿主体内的成年鼠类宿主与体内相互作用进行解剖和有针对性的操纵，并对其对免疫产生影响。我们认为，使用这些新的可用工具对LM感染的新生儿免疫反应的分析将不仅对新生儿LM感染，而且对疫苗设计产生重要的机械见解。 我们假设a）在新生儿可以产生提供对LM感染的保护性免疫的主要效应子和记忆T细胞； b）主要是新生儿抗原表现的赤字，导致新生儿对原发性LM感染的敏感性增强； c）正是新生儿特异性的调节途径，为响应LM感染或疫苗接种而在新生儿中提供了机械基础，以使功能记忆T细胞产生失败。为了检验这些假设，我们将成功采用成人LM感染和疫苗接种的方法，并将这些工具应用于新生儿。类似于LM感染对成年小鼠免疫学知识的巨大影响，我们认为我们的研究将解决并引起新生儿免疫学和疫苗学中的基本问题。