A Study of Heterologous Immunity Induced by Neonatal BCG Vaccination

新生儿卡介苗接种诱导异源免疫的研究

• 批准号: 8191744
• 负责人: Daniel H. Libraty
• 金额: $ 24.68万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8191744
• 关键词: Antibody Formation; Attenuated; Biological Assay; Birth; Blood specimen; Calmette-Guerin Bacillus; Cell physiology; Cessation of life; Child health care; Clinical; Clinical Research; Communicable Diseases; Dengue; Dengue Virus; Development; Dose; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Foundations; Goals; Hepatitis B Vaccination; Human; Human poliovirus; Immune; Immune response; Immune system; Immunity; Immunoglobulin G; Immunology; Individual; Infant; Infant Health; Infant Mortality; Knowledge; Lead; Life; Measures; Morbidity - disease rate; Neonatal; Nested Case-Control Study; Newborn Infant; Oral; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Play; Predisposition; Recording of previous events; Reporting; Role; Sampling; Shapes; T-Lymphocyte; Tetanus Toxoid; Tuberculosis; Vaccination; Vaccine Antigen; Vaccines; Virus Diseases; critical period; design; global health; improved; infancy; mortality; mycobacterial; neonate; novel strategies; pathogen; prospective; response; vaccination strategy

DESCRIPTION (provided by applicant): Infectious diseases are a major cause of global morbidity and mortality in neonates and infants. The heightened susceptibility to infectious diseases over the first year of life, and difficulties inducing rapid and protective vaccine responses, are largely due to an immature immune system. Significant gaps in knowledge exist in understanding how to enhance protective immune responses soon after birth and throughout infancy. There is growing recognition that an individual's immune response to one pathogen can be shaped by the prior exposure history to unrelated pathogens, and this has been termed heterologous immunity. Heterologous immune responses are likely to play a significant role in shaping and maturing the malleable immune system over neonatal life and early infancy. Bacillus Calmette-Guerin (BCG) is a live attenuated mycobacterial vaccine typically given within the first two weeks of life, and it is the most widely used vaccine in the world. In addition to providing clinical protection against disseminated forms of tuberculosis, BCG vaccination has also been reported to reduce overall infant mortality and suggested to have beneficial heterologous immune effects. The specific aim of this exploratory proposal is to delineate if neonatal BCG vaccination alters the specific immune responses to subsequent unrelated infant vaccines. The proposed study will begin to delineate heterologous immune effects of neonatal BCG vaccination. A nested case-control study will be conducted comparing T-cell and antibody responses to the first (priming) doses of tetanus toxoid, live attenuated oral polio virus, and hepatitis B vaccination in infants with prior neonatal BCG vaccination and those without neonatal BCG vaccination. The study will utilize existing peripheral blood mononuclear cells (PBMC) and plasma samples that have been collected as part of an ongoing prospective clinical study of dengue virus infections during infancy. The existing blood samples are from infants without dengue virus infections and would not otherwise be used in the dengue study. Vaccine antigen-specific T-cell functions and phenotypes will be assessed by state-of-the-art flow cytometry assays in the PBMC samples. IgG antibody responses will be measured by ELISA in the plasma samples. The findings in this exploratory study will support the development of a more definitive study to delineate the effects and underlying mechanisms of heterologous immunity in neonates and infants. This proposal is a first step towards a better understanding of human immunology in the newborn and developing new approaches to neonatal and infant vaccination. Expanding and improving the ability to induce protective immunity against infectious diseases in the first few months of life will have a significant impact on global health. PUBLIC HEALTH RELEVANCE: Infectious diseases are a major cause of severe illness and death in newborns and infants around the world. Newborns and infants have a heightened susceptibility to infectious diseases, and poor responses to vaccines, due to an immature immune system. A better understanding of the factors that shape neonatal and infant immune responses can lead to new vaccination strategies and improved global infant and child health.

描述（由申请方提供）：传染病是全球新生儿和婴儿发病率和死亡率的主要原因。在生命的第一年，对传染病的易感性增加，以及难以诱导快速和保护性的疫苗反应，主要是由于免疫系统不成熟。在了解如何在出生后不久和整个婴儿期增强保护性免疫反应方面存在重大知识差距。 越来越多的人认识到，一个人对一种病原体的免疫反应可以通过先前暴露于不相关病原体的历史来塑造，这被称为异源免疫。异源免疫反应可能在新生儿和婴儿早期可塑性免疫系统的塑造和成熟方面发挥重要作用。卡介苗（BCG）是一种减毒活分枝杆菌疫苗，通常在出生后的前两周内接种，是世界上使用最广泛的疫苗。除了提供针对播散型结核病的临床保护外，BCG疫苗接种还被报道降低总体婴儿死亡率，并被认为具有有益的异源免疫效应。 本探索性建议的具体目的是描述新生儿卡介苗接种是否会改变对后续不相关婴儿疫苗的特异性免疫应答。拟议的研究将开始描述新生儿卡介苗接种的异源免疫效应。将进行一项巢式病例对照研究，比较既往接种过新生儿BCG疫苗和未接种过新生儿BCG疫苗的婴儿对破伤风类毒素、口服脊髓灰质炎减毒活病毒和乙型肝炎B疫苗首次（初免）接种的T细胞和抗体应答。该研究将利用现有的外周血单核细胞（PBMC）和血浆样本，这些样本是作为正在进行的婴儿期登革热病毒感染前瞻性临床研究的一部分收集的。现有的血液样本来自没有登革热病毒感染的婴儿，否则不会用于登革热研究。将通过PBMC样本中最先进的流式细胞术测定评估疫苗抗原特异性T细胞功能和表型。将通过ELISA测定血浆样本中的IgG抗体应答。这项探索性研究的结果将支持开发一项更明确的研究，以描述新生儿和婴儿异源免疫的影响和潜在机制。该提案是更好地了解新生儿人类免疫学和开发新生儿和婴儿疫苗接种新方法的第一步。扩大和提高在生命最初几个月诱导针对传染病的保护性免疫的能力将对全球健康产生重大影响。 公共卫生相关性：传染病是世界各地新生儿和婴儿严重疾病和死亡的主要原因。由于免疫系统不成熟，新生儿和婴儿对传染病的易感性较高，对疫苗的反应较差。更好地了解影响新生儿和婴儿免疫反应的因素，可以制定新的疫苗接种战略，改善全球婴儿和儿童健康。