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.

项目概要 SARS-CoV-2，因其引起的疾病而通常被称为 COVID-19，已感染超过 410 万人， 包括超过 240,000 例死亡，尽管儿童中的 COVID-19 病理被认为相对较轻。 对于成人来说，大约 10% 的婴儿患有严重的 COVID-19 疾病，需要高级护理，并且 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，因此婴儿和青少年 显然，儿童可能是 SARS-CoV-2 大量传播的罪魁祸首 (5-7)。 婴儿的一种潜在保护机制仍然是被动的。 以前感染过的母亲通过母乳喂养提供的免疫力，并且如果 SARS-CoV-2 抗体 (Ab) 牛奶中的反应很有效，这些抗体作为 COVID-19 治疗剂可能非常有益。 可能通过提供分泌型 IgA 和 sIgM Ab（主要抗体成分）来有效治疗 COVID-19 牛奶中的 s 类抗体能够抵抗蛋白水解降解，并且可能在呼吸系统中具有高度功能。 牛奶中几乎所有 sIgA/sIgM 均来自粘膜免疫系统，包括呼吸道。 因此，我们应该预期会出现 SARS-CoV-2 反应性 sIgA/sIgM 反应，尽管其幅度 因此，SARS-CoV-2 反应性牛奶抗体必须 为了实现这一目标，我们已经对其潜在的治疗和保护功效进行了全面研究。 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。 使用 15 个样本的试点数据发现，93% 在 COVID-19 后获得的样本含有 SARS-CoV-2 反应性 sIgA 抗体。 基于这一早期证据，我们提出的项目旨在： (a) 测量 SARS-CoV-2 反应性抗体 (b) 确定中和能力 (c) 评估这些 Ab 的非中和性、Fc 介导的功能。 综合研究将确定牛奶中的新冠病毒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“恢复期”提供基础。 牛奶抗体的功效研究，其影响超出了大流行范围，有助于填补相对较大的空白 有关母乳免疫学的知识差距。