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氏菌（LM）是新生儿的主要病原体。 LM 还被开发为从 HIV 到肿瘤等异源疫苗的疫苗载体。大多数疫苗将接种给婴儿。然而，对于新生儿或婴儿对 LM 的免疫反应却知之甚少。更令人惊讶的是，因为LM感染是免疫学中研究得最好的模型之一，并且已经产生了优秀的工具，可以对成年鼠宿主微生物的体内相互作用及其对免疫的影响进行解剖和有针对性的操作。我们相信，利用这些新可用的工具分析新生儿对 LM 感染的免疫反应，不仅将为新生儿 LM 感染，而且为疫苗设计提供重要的机制见解。 我们假设 a) 新生儿中可以产生初级效应细胞和记忆 T 细胞，为 LM 感染提供保护性免疫； b) 主要是新生儿抗原呈递缺陷导致新生儿对原发性LM感染的易感性增加； c) 新生儿特异性调节途径为新生儿因 LM 感染或疫苗接种而无法生成功能性记忆 T 细胞提供了机制基础。为了检验这些假设，我们将采用成人 LM 感染和疫苗接种研究中成功采用的方法，并将这些工具应用于新生儿。与 LM 感染研究对成年小鼠免疫学知识产生的巨大影响类似，我们相信我们的研究将解决并揭示新生儿免疫学和疫苗学的基本问题。