Arsenic and immune response to influenza vaccination in pregnant women and newborns

孕妇和新生儿的砷与流感疫苗接种的免疫反应

• 批准号: 10066262
• 负责人: Christopher D Heaney
• 金额: $ 60.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10066262
• 关键词: Address; Affect; Antibody Avidity; Antibody Response; Antibody titer measurement; Area; Arsenic; Bangladesh; Biological; Birth; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Carbon; Cells; Child Nutrition; Childhood; Clinical; Data; Developmental Toxicant; Dose; Enrollment; Environmental Exposure; Exposure to; Folic Acid; Future; Health; Hepatitis E virus; Human; Immune response; Immunity; Immunoglobulin A; Immunoglobulin G; Impairment; Influenza; Influenza vaccination; Interferon Type II; Interleukin-1 beta; Interleukin-2; Intervention; Joints; Knowledge; Lead; Life; Longitudinal Studies; Malnutrition; Maternal and Child Health; Maternal antibody; Measures; Mediating; Mediator of activation protein; Metabolism; Micronutrients; Mission; Morbidity - disease rate; Mothers; National Institute of Environmental Health Sciences; Neonatal; Newborn Infant; Outcome; Pathogenicity; Pathway interactions; Peripheral Blood Lymphocyte; Population; Postpartum Period; Pregnancy; Pregnant Women; Public Health; Regimen; Research; Research Project Grants; Respiratory Tract Infections; Risk Factors; Secondary Immunization; Serum; Site; System; TNF gene; Testing; Time; Toxic effect; Tuberculosis; Vaccination; Vaccines; Viral; Vitamin B 12; Woman; Work; base; cohort; cytokine; design; gastrointestinal infection; immune activation; immune function; immunotoxicity; improved; infection risk; innovation; insight; maternal vaccination; micronutrient deficiency; novel; novel vaccines; pathogen; prevent; respiratory; respiratory morbidity; response; seroconversion; urinary; vaccine access; vaccine-induced antibodies; vaccine-induced immunity

PROJECT SUMMARY/ABSTRACT. There is a fundamental gap in understanding of whether arsenic, a known developmental toxicant, alters maternal immune responses to vaccination and whether exposure to arsenic during pregnancy impairs the transfer of maternal vaccine-induced antibody to the newborn. Moreover, factors known to affect arsenic metabolism and toxicity outcomes, particularly micronutrients critical in one-carbon metabolism, have not been evaluated in studies of arsenic immunotoxicity and vaccine-induced protection in mothers and their newborns. Continued existence of this gap represents an important problem because, until it is filled, optimal points for intervention to prevent arsenic-related immunotoxicity and morbidity during pregnancy and early life will not be known. Our objective is to investigate how maternal arsenic exposure and one-carbon metabolism micronutrient deficiencies alter maternal and newborn influenza antibody titer and avidity, respiratory morbidity, and measures of systemic immune function following maternal influenza vaccination. Our hypothesis is that maternal arsenic exposure and one-carbon metabolism micronutrient deficiencies can alter maternal and newborn influenza antibody titer and avidity, respiratory morbidity, and systemic immune function following influenza vaccination during pregnancy. The rationale for the proposed research is that studying the effects of arsenic exposure on antibody response to vaccination and on immune function could provide insight into mechanisms of human arsenic immunotoxicity and inform new vaccine regimens (higher doses; booster immunizations) to restore protection in arsenic-exposed and malnutrition- affected populations worldwide. Our hypothesis is informed by preliminary findings of associations between maternal arsenic exposure, viral seroconversion, and measures of systemic immune activation in an established pregnancy surveillance system in Bangladesh. Within a cohort of 400 pregnant women and their newborns, we will test our hypothesis by pursuing three specific aims: 1) Establish whether maternal arsenic exposure during pregnancy alters maternal and newborn influenza antibody titer and avidity following maternal influenza vaccination; 2) Determine the association of arsenic exposure with respiratory morbidity in pregnant women and their newborns and whether vaccine-specific and/or systemic immune function mediate this association; and 3) Assess whether arsenic exposure and one-carbon metabolism micronutrient deficiencies during pregnancy have a joint effect on vaccine-specific and/or systemic immune function and respiratory illness in mothers and their newborns. The approach is innovative because it is designed to challenge and shift current research paradigms on the human health consequences of arsenic immunotoxicity. Results from this work will represent a significant advancement in understanding of the extent to which arsenic exposure and one-carbon metabolism micronutrient deficiencies during pregnancy alter maternal and newborn immune response and morbidity following maternal influenza-vaccination.

项目摘要/摘要。对于砷是否是一种已知的物质，人们的理解存在着根本性的差距。 发育毒物，改变母体对疫苗接种的免疫反应以及是否接触砷 怀孕期间会损害母体疫苗诱导的抗体向新生儿的转移。此外，因素 已知会影响砷代谢和毒性结果，特别是在一碳中至关重要的微量营养素 砷的免疫毒性和疫苗诱导保护的研究尚未评估 母亲和她们的新生儿。这种差距的持续存在是一个重要的问题，因为，直到它 已填满，干预期间预防砷相关免疫毒性和发病率的最佳点 怀孕和早年生活将不为人知。我们的目标是调查母亲的砷暴露和 一碳代谢微量营养素缺乏会改变孕产妇和新生儿流感抗体滴度， 孕产妇流感后的亲和力、呼吸道发病率和全身免疫功能的测量 疫苗接种。我们的假设是，母亲的砷暴露和一碳代谢微量营养素 缺陷可能会改变孕产妇和新生儿流感抗体滴度和亲和力、呼吸道疾病发病率和 妊娠期间接种流感疫苗后的全身免疫功能。拟议的理由 研究的目的是研究砷暴露对疫苗接种抗体反应和免疫的影响 功能可以深入了解人类砷免疫毒性的机制并为新疫苗提供信息 方案（更高剂量；加强免疫）以恢复砷暴露和营养不良的保护- 全世界受影响的人群。我们的假设是基于以下关联的初步发现： 母体砷暴露、病毒血清转化以及全身免疫激活的测量 孟加拉国建立了妊娠监测系统。在 400 名孕妇及其她们的队列中 对于新生儿，我们将通过追求三个具体目标来检验我们的假设：1）确定母亲是否患有砷 怀孕期间的暴露会改变孕产妇和新生儿流感抗体的滴度和亲和力 流感疫苗接种； 2) 确定砷暴露与妊娠期呼吸道疾病发病率的关系 妇女及其新生儿以及疫苗特异性和/或全身免疫功能是否介导这种情况 协会; 3) 评估砷暴露和一碳代谢微量营养素是否缺乏 怀孕期间对疫苗特异性和/或全身免疫功能和呼吸系统有联合影响 母亲及其新生儿的疾病。这种方法是创新的，因为它旨在挑战和转变 当前关于砷免疫毒性对人类健康影响的研究范式。结果由此 这项工作将代表着对砷暴露和砷暴露程度的理解取得了重大进展。 怀孕期间一碳代谢微量营养素缺乏会改变孕产妇和新生儿的免疫 孕产妇流感疫苗接种后的反应和发病率。

项目成果

Application of Markov models to predict changes in nasal carriage of Staphylococcus aureus among industrial hog operations workers.

• DOI: 10.1080/15459624.2022.2025998
• 发表时间: 2022-03
• 期刊: Journal of occupational and environmental hygiene
• 影响因子: 2
• 作者: Edmondson MG;Heaney CD;Davis MF;Ramachandran G
• 通讯作者: Ramachandran G

Assessing Residential Exposure to Microbes from Industrial Hog Operations in Rural North Carolina: Methods and Lessons Learned.

评估北卡罗来纳州农村地区住宅对工业生猪养殖微生物的暴露：方法和经验教训。

• DOI: 10.1353/cpr.2022.0006
• 发表时间: 2022
• 期刊: Progress in community health partnerships : research, education, and action
• 作者: Coffman,VanessaR;Hall,DevonJ;Pisanic,Nora;Wiesner-Friedman,Corinne;Rogers,Shane;Rule,Ana;McCormack,Meredith;Diener-West,Marie;Davis,MeghanF;Heaney,ChristopherD
• 通讯作者: Heaney,ChristopherD

COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva.

• DOI: 10.1128/jcm.02204-20
• 发表时间: 2020-12-17
• 期刊: Journal of clinical microbiology
• 影响因子: 9.4
• 作者: Pisanic N;Randad PR;Kruczynski K;Manabe YC;Thomas DL;Pekosz A;Klein SL;Betenbaugh MJ;Clarke WA;Laeyendecker O;Caturegli PP;Larman HB;Detrick B;Fairley JK;Sherman AC;Rouphael N;Edupuganti S;Granger DA;Granger SW;Collins MH;Heaney CD
• 通讯作者: Heaney CD

Community-driven research and capacity building to address environmental justice concerns with industrial air pollution in Curtis Bay, South Baltimore.

社区驱动的研究和能力建设，以解决南巴尔的摩柯蒂斯湾工业空气污染的环境正义问题。

• DOI: 10.3389/fepid.2023.1198321
• 发表时间: 2023
• 期刊: Frontiers in epidemiology
• 作者: Aubourg,MatthewA;Sawtell,Greg;Deanes,Lauren;Fabricant,Nicole;Thomas,Meleny;Spicer,Kristoffer;Wagar,Caila;Campbell,Shashawnda;Ulman,Abigail;Heaney,ChristopherD
• 通讯作者: Heaney,ChristopherD

Immune Response Characterization after Controlled Infection with Lyophilized Shigella sonnei 53G.

• DOI: 10.1128/msphere.00988-19
• 发表时间: 2020-09-23
• 期刊: mSphere
• 影响因子: 4.8
• 作者: Clarkson KA;Frenck RW Jr;Dickey M;Suvarnapunya AE;Chandrasekaran L;Weerts HP;Heaney CD;McNeal M;Detizio K;Parker S;Hoeper A;Bourgeois AL;Porter CK;Venkatesan MM;Kaminski RW
• 通讯作者: Kaminski RW