Breast Milk Microbiota Influence on Infant Immunity and Growth (BEAMING) ADMINISTRATIVE SUPPLEMENT

母乳微生物群对婴儿免疫和生长的影响 (BEAMING) 行政补充材料

• 批准号: 10631019
• 负责人: Alash'le G. Abimiku
• 金额: $ 10.42万
• 依托单位: INSTITUTE OF HUMAN VIROLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10631019
• 关键词: Administrative Supplement; Affect; African; Alleles; Antibody titer measurement; Antigens; Biological; Breast Feeding; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 pandemic; Child; Childhood; Country; Data; Exclusive Breastfeeding; Family member; Genes; Genetic Determinism; Grant; Growth; HIV; HIV-exposed uninfected infant; Health; Hour; Human Milk; Immune; Immune response; Immunity; Infant; Inherited; Laboratories; Life; Microbial Genetics; Milk; Mothers; Newborn Infant; Nigeria; Play; Population; Process; Reagent; Role; Sampling; Ships; Site; South Africa; Specimen; Structure; Testing; Time; Vaccination; Vaccines; Variant; Work; base; cohort; conditioning; coronavirus disease; cost; experience; genetic variant; gut bacteria; gut microbiota; infant gut microbiome; insight; man; metabolome; microbial; microbiome; microbiota; stool sample; vaccine response; vaccine-induced antibodies

ABSTRACT Understanding microbial shifts and how they affect vaccine response is central to this study. We will determine if gut microbial communities associated with breastfeeding in the HEU infant follows the same successional trajectory as HU controls and resolve the differences at functional level. How the continuous conditioning of the infant gut by the microbiota from the breast milk affects the infant microbiome and subsequent immune responses to pediatric vaccination is not known and would also be studied in this submission. Teasing out possible humoral vaccine differences due to HLA associations will be an important component to consider when identifying the mechanism and impact of microbial ecological conditioning through the breast milk towards vaccine responsiveness. Our submission proposes to use biological samples collected at regular intervals over a 12-month period from a multi-site study of well characterized cohort of mother: infant pairs of HEU and HU controls from Nigeria and South Africa to investigate both host and microbial genetic determinants of altered immunity in African infants. However, the COVID-19 pandemic that hit in 2021 however disrupted our work for about 18 months since the laboratories were closed under lockdown in addition to challenges due to hike in cost of laboratory consumables and reagents, delay and cancellation of shipments, and loss of man hours due to ill health of staff and family members due to COVID-19. Our administrative supplemental submission is to request for an extension from 1 July 2023 to 30 June 2023 to continue to investigate microbial shifts and how they affect growth and immune response to pediatric vaccines in HEU infants as compared to matched HU controls. Our hypothesis is that breast milk microbiota conditioning in newborn infants impacts growth and immune responsiveness to pediatric vaccines in the context of inherited HLA variants. We will continue to test our hypothesis through the same specific aims: Aim 1: Compare the ontogeny of microbial structure and metabolome in longitudinal breast milk and stool samples of corresponding 200 Exclusively Breast Fed (EBF) HEU versus 100 EBF HU control, infants over the first 12 months of life to document influence of the milk microbiota on the infant gut microbiome; and their collective effect or association with growth. Aim 2: Assess the relationship between infant microbial structure and humoral immune responses to pediatric vaccines AIM 3: To associate inherited HLA gene variants with humoral immune responses to pediatric vaccines in the two infant groups. This proposal will interrogate both host and microbial genetic determinants of altered immunity in HEU and is therefore highly relevant and responsive to the original RFA RM16-013.

抽象的 了解微生物变化及其如何影响疫苗反应是本研究的核心。我们将 确定 HEU 婴儿中与母乳喂养相关的肠道微生物群落是否遵循相同的规律 HU 在功能层面控制和解决差异的连续轨迹。如何连续 母乳中的微生物群对婴儿肠道的调理会影响婴儿微生物组， 对儿科疫苗接种的后续免疫反应尚不清楚，也将在本研究中进行研究 提交。梳理出由于 HLA 关联导致的体液疫苗可能存在的差异将是一个重要的研究 确定微生物生态调节的机制和影响时要考虑的组成部分 通过母乳获得疫苗反应。我们的意见书建议使用生物 在 12 个月的时间内定期从多地点研究中收集的样本 母亲队列：来自尼日利亚和南非的 HEU 和 HU 婴儿对进行对照，以调查两个宿主 以及非洲婴儿免疫力改变的微生物遗传决定因素。然而，新冠肺炎 (COVID-19) 大流行 然而，自 2021 年实验室因疫情关闭而关闭以来，我们的工作中断了约 18 个月。 除了由于实验室消耗品和试剂成本上涨、延误和 由于新冠肺炎 (COVID-19) 疫情，员工和家人健康状况不佳，导致发货取消和工时损失。 我们的行政补充意见书要求将2023年7月1日延长至6月30日 2023 年继续研究微生物变化及其如何影响儿科的生长和免疫反应 与匹配的 HU 对照相比，HEU 婴儿接种的疫苗。我们的假设是母乳微生物群 新生儿的体质调节会影响儿童的生长和对儿科疫苗的免疫反应 遗传性 HLA 变异的背景。 我们将继续通过相同的具体目标来检验我们的假设： 目标 1：纵向比较母乳和粪便中微生物结构和代谢组的个体发育 相应 200 个纯母乳喂养 (EBF) HEU 与 100 个 EBF HU 对照的样本，婴儿超过 生命的前 12 个月，记录乳汁微生物群对婴儿肠道微生物群的影响；和他们的 集体效应或与增长的关联。 目标 2：评估婴儿微生物结构与儿科体液免疫反应之间的关系 疫苗 目标 3：将遗传性 HLA 基因变异与儿科疫苗的体液免疫反应联系起来 两个婴儿组。 该提案将探讨 HEU 中免疫改变的宿主和微生物遗传决定因素，并且是 因此与原始 RFA RM16-013 高度相关并响应。

项目成果

Characterization of the novel HLA-DQB1*05:272 allele in a South African patient by next-generation sequencing.

通过新一代测序对南非患者的新型 HLA-DQB1*05:272 等位基因进行表征。

• 发表时间: 2021
• 影响因子: 8
• 作者: Valley;Maart, Shireen;Seele, Karen;Gray, Clive M
• 通讯作者: Gray, Clive M

Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses.

南非和尼日利亚婴儿的纵向肠道微生物群组成与破伤风疫苗反应的关系。

• 发表时间: 2023-07-03
• 作者: Iwase, Saori C;Jaspan, Heather B;Happel, Anna;Holmes, Susan P;Abimiku, Alash'le;Osawe, Sophia;Gray, Clive M;Blackburn, Jonathan M
• 通讯作者: Blackburn, Jonathan M