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

对人乳中的 SARS-CoV-2 反应性抗体进行全面评估，以确定其作为 COVID-19 治疗药物和预防母乳喂养婴儿感染的手段的潜力

• 批准号: 10240336
• 负责人: Rebecca Powell
• 金额: $ 66.81万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-14 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240336
• 关键词: 2019-nCoV; Adult; Alternative Complement Pathway; Antibodies; Antibody Response; Antiviral Agents; Binding; Biological; Biological Assay; Biological Process; Breast Feeding; COVID-19; COVID-19 pandemic; COVID-19 therapeutics; COVID-19 treatment; Caring; Cells; Cessation of life; Child; Data; Deposition; Disease; Enrollment; Foundations; Gastrointestinal tract structure; Human Milk; Immune response; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Immunology; Infant; Infection; Infection prevention; Inflammatory; Knowledge; Lactation; Lectin; Link; Lung; Measures; Mediating; Milk; Mothers; Mucosal Immune System; Mucous Membrane; Multisystem Inflammatory Syndrome in Children; Nature; Participant; Passive Immunity; Pathology; Population; Preparation; Proteins; Reporting; Research; Resistance; Respiratory System; SARS-CoV-2 antibody; SARS-CoV-2 infection; SARS-CoV-2 inhibitor; SARS-CoV-2 spike protein; Sampling; Secretory Immunoglobulin A; Serum; Source; Symptoms; Therapeutic; Therapeutic Uses; Therapeutic antibodies; Tissues; Treatment Efficacy; Viral Physiology; Virus Diseases; Work; antibody-dependent cellular phagocytosis; base; complement pathway; donor milk; efficacy study; experience; high throughput screening; neutrophil; novel coronavirus; pandemic disease; prevent; protective efficacy; recruit; respiratory; response; severe COVID-19

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.

项目摘要 SARS-COV-2通常被称为Covid-19，因为它引起的疾病，已感染了410万人， 包括> 240,000人死亡。尽管据信儿童的COVID-19与儿童的病理相比相对温和 对于成年人，大约10％的基础设施经历了严重的Covid-199需要高级护理的疾病，并且 最近，在Covid-19和最近发生严重的炎症性疾病之间发生了可能的联系 称为“小儿多系统炎症综合征与COVID-19的时间相关”（1-4）。 此外，由于199症状似乎与传播，婴儿和年轻人无关 儿童可能负责大量的SARS-COV-2传播（5-7）。显然，保护 感染的人群仍然至关重要。婴儿的一种潜在保护机制是被动 先前感染的母亲通过母乳喂养提供免疫力，如果SARS-COV-2抗体 （AB）牛奶中的反应是潜在的，这些ABS可能是一种COVID-19疗法，可能是非常有益的。这些牛奶腹肌 可以通过提供分泌的IgA和Sigm ABS（主要的AB组件）来有效治疗Covid-19 在牛奶中。 S类的ABS对蛋白水解降解具有抗性，并且可能在呼吸道 组织（2，6）。牛奶中几乎所有的Siga/Sigm均来自粘膜免疫系统，包括呼吸系统 道因此，我们应该期望SARS-COV-2反应的SIGA/SIGM响应，尽管大小，但 功能和此响应的耐用性仍然未知。因此，必须 全面研究其潜在的治疗和受保护的效率。朝向这个目标，我们有 招募了1600多名哺乳参与者，其中包括600多名从Covid-19疾病中恢复过来。我们的 使用15个样品的试点数据发现93％在covid-19中含有SARS-COV-2反应性SIGA ABS。 基于此早期证据，我们提出的项目打算：（a）测量SARS-COV-2反应性ABS 感染后的牛奶和这种反应的长期耐用性； （b）确定神经元化能力 这些腹肌； （c）评估这些ABS的非中和，FC介导的功能。这 全面的研究将确定牛奶中的covid19特异性ABS是否具有保护生物学功能和 应该被视为理论ABS的来源。这些数据将为“康复 牛奶AB的效率研究，并且具有超出大流行的影响，以填补相对较大的 关于人乳免疫学的知识差距。