Comprehensive assessment of SARS-CoV-2-reactive antibodies in human milk to determine their potential as a COVID-19 therapeutic and as a means to prevent infection of breastfed babies
Comprehensive assessment of SARS-CoV-2-reactive antibodies in human milk to determine their potential as a COVID-19 therapeutic and as a means to prevent infection of breastfed babies
批准号:
10240336
负责人:
Rebecca Powell
金额:
$66.81万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-14 至 2023-07-31
关键词:
2019-nCoVAdultAlternative Complement PathwayAntibodiesAntibody ResponseAntiviral AgentsBindingBiologicalBiological AssayBiological ProcessBreast FeedingCOVID-19COVID-19 pandemicCOVID-19 therapeuticsCOVID-19 treatmentCaringCellsCessation of lifeChildDataDepositionDiseaseEnrollmentFoundationsGastrointestinal tract structureHuman MilkImmune responseImmunityImmunoglobulin AImmunoglobulin GImmunoglobulin MImmunoglobulinsImmunologyInfantInfectionInfection preventionInflammatoryKnowledgeLactationLectinLinkLungMeasuresMediatingMilkMothersMucosal Immune SystemMucous MembraneMultisystem Inflammatory Syndrome in ChildrenNatureParticipantPassive ImmunityPathologyPopulationPreparationProteinsReportingResearchResistanceRespiratory SystemSARS-CoV-2 antibodySARS-CoV-2 infectionSARS-CoV-2 inhibitorSARS-CoV-2 spike proteinSamplingSecretory Immunoglobulin ASerumSourceSymptomsTherapeuticTherapeutic UsesTherapeutic antibodiesTissuesTreatment EfficacyViral PhysiologyVirus DiseasesWorkantibody-dependent cellular phagocytosisbasecomplement pathwaydonor milkefficacy studyexperiencehigh throughput screeningneutrophilnovel coronaviruspandemic diseasepreventprotective efficacyrecruitrespiratoryresponsesevere COVID-19
中文摘要
项目摘要
SARS-CoV-2,通常被称为COVID-19,因为它引起的疾病,已经感染了超过410万人,
死亡人数超过24万人。尽管与其他疾病相比,儿童的COVID-19病理学被认为相对温和,
对于成年人,大约10%的婴儿患有严重的COVID-19疾病,需要高级护理,
最近,有报道称,COVID-19与一种严重的炎症性疾病之间可能存在联系
称为“与COVID-19暂时相关的儿科多系统炎症综合征”(1-4)。
此外,由于COVID-19症状似乎与传染性无关,
儿童可能是导致SARS-CoV-2传播的主要原因(5-7)。显然,保护
这一人群免受感染仍然至关重要。婴儿的一种潜在的保护机制是被动的
免疫力提供通过母乳喂养由以前感染的母亲,如果SARS-CoV-2抗体
(Ab)由于这些抗体在牛奶中的反应是有效的,因此这些抗体作为COVID-19治疗剂可能非常有益。这些牛奶腹肌
可能通过提供分泌型伊加和sIgM抗体(主要抗体成分)有效治疗COVID-19
在牛奶里。s类抗体对蛋白水解降解具有抗性,并且可能在呼吸系统中具有高度功能。
组织(2,6)。乳汁中几乎所有的sIgA/sIgM都来源于粘膜免疫系统,包括呼吸道免疫系统。
道;因此,我们应该期待SARS-CoV-2反应性sIgA/sIgM反应,尽管幅度,
这种反应的功能性和持久性仍然未知。因此,SARS-CoV-2反应性牛奶抗体必须
全面研究其潜在的治疗和保护功效。为了实现这一目标,我们
招募了1600多名哺乳期参与者,其中600多名已从COVID-19疾病中康复。我们
使用15个样本的试点数据发现,COVID-19后获得的93%含有SARS-CoV-2反应性sIgA Ab。
基于这一早期证据,我们提出的项目打算:(a)测量SARS-CoV-2反应性抗体,
(B)测定感染后的牛奶中和能力和这种应答的长期持久性;
(c)评估这些Ab的非中和性、Fc介导的功能性。这
全面的研究将确定牛奶中的COVID 19特异性抗体是否具有保护性生物功能,
应被视为治疗性抗体的来源。这些数据将为“康复”提供基础
牛奶抗体的功效研究,并具有超越大流行的影响,有助于填补一个相对较大的
关于母乳免疫学的知识差距。
英文摘要
Project Summary
SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >4.1 million people,
including >240,000 deaths. Though COVID-19 pathology in children is believed to be relatively mild compared
to adults, approximately 10% of infants experience severe COVID-19 illness requiring advanced care, and
recently, a possible link has been reported between COVID-19 and a serious inflammatory disease recently
termed “Pediatric Multi-System Inflammatory Syndrome Temporally Associated with COVID-19” (1-4).
Furthermore, as COVID-19 symptoms do not appear to correlate with transmissibility, infants and young
children are likely responsible for a significant amount of SARS-CoV-2 dissemination (5-7). Clearly, protecting
this population from infection remains essential. One potential mechanism of protection in babies is the passive
immunity provided through breastfeeding by a previously-infected mother, and if the SARS-CoV-2 antibody
(Ab) response in milk is potent, these Abs may be highly beneficial as a COVID-19 therapeutic. These milk Abs
may be effective in treating COVID-19 by providing secretory (s) IgA and sIgM Abs, the major Ab components
in milk. Abs of the s class are resistant to proteolytic degradation and likely highly functional in respiratory
tissue (2, 6). Nearly all sIgA/sIgM in milk is derived from the mucosal immune system, including the respiratory
tract; therefore, we should expect a SARS-CoV-2-reactive sIgA/sIgM response, though the magnitude,
functionality, and durability of this response remains unknown. As such, SARS-CoV-2-reactive milk Abs must
be comprehensively studied for their potential therapeutic and protective efficacy. Towards that aim, we have
recruited over 1600 lactating participants, including over 600 who have recovered from COVID-19 illness. Our
pilot data using 15 samples found 93% obtained post-COVID-19 contain SARS-CoV-2-reactive sIgA Abs.
Based on this early evidence, our proposed project intends to: (a) Measure the SARS-CoV-2-reactive Abs in
milk following infection and the long-term durability of this response; (b) Determine the neutralization capacity
of these Abs; and (c) Evaluate the non-neutralizing, Fc-mediated functionality of these Abs. This
comprehensive research will determine if COVID19-specific Abs in milk have protective biologic functions and
should be considered as a source of therapeutic Abs. These data would provide a foundation for ‘convalescent
milk Ab’ efficacy studies, and have implications beyond the pandemic, serving to fill a relatively large
knowledge gap regarding human milk immunology.
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专著(0)
科研奖励(0)
会议论文
Comprehensive assessment of SARS-CoV-2-reactive antibodies in human milk to determine their potential as a COVID-19 therapeutic and as a means to prevent infection of breastfed babies
-
批准号:10470802
-
项目类别:
-
资助金额:$57.29万
-
财政年份:2020
-
负责人:Rebecca Powell
-
依托单位:
Antibody-dependent cellular phagocytosis by human breastmilk leukocytes: impact of antibody class, stage of lactation, and target size
-
批准号:10222911
-
项目类别:
-
资助金额:$6.39万
-
财政年份:2020
-
负责人:Rebecca Powell
-
依托单位:
Comprehensive assessment of SARS-CoV-2-reactive antibodies in human milk to determine their potential as a COVID-19 therapeutic and as a means to prevent infection of breastfed babies
-
批准号:10177618
-
项目类别:
-
资助金额:$79.34万
-
财政年份:2020
-
负责人:Rebecca Powell
-
依托单位:
Antibody-dependent cellular phagocytosis by human breastmilk leukocytes: impact of antibody class, stage of lactation, and target size
-
批准号:9789908
-
项目类别:
-
资助金额:$21.19万
-
财政年份:2018
-
负责人:Rebecca Powell
-
依托单位:
海外基金