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: 10470802
• 负责人: Rebecca Powell
• 金额: $ 57.29万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470802
• 关键词: 2019-nCoV; Adult; Alternative Complement Pathway; Antibodies; Antibody Response; 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; Persons; 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; post SARS-CoV-2 infection; post-COVID-19; 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，通常被称为新冠肺炎，因为它引起的疾病，已经感染了410万人。 其中包括24万人死亡。尽管儿童新冠肺炎的病理被认为是相对轻微的 对于成年人来说，大约10%的婴儿患有严重的新冠肺炎疾病，需要高级护理，并且 最近，有报道称新冠肺炎可能与一种严重的炎症性疾病有关 称为“儿童多系统炎症综合征暂时性新冠肺炎”(1-4)。 此外，由于新冠肺炎症状似乎与传染性无关，因此婴幼儿 儿童可能是SARS-CoV-2传播的主要原因(5-7)。显然，保护 这些免受感染的人口仍然是必不可少的。婴儿的一种潜在的保护机制是被动的 以前感染过病毒的母亲通过母乳喂养提供的免疫力，如果SARS-CoV-2抗体 (AB)牛奶中的反应是有效的，这些抗体作为新冠肺炎疗法可能是非常有益的。这些牛奶粉 可能通过提供分泌型(S)免疫球蛋白A和SIgM抗体而有效治疗新冠肺炎，这是主要的抗体成分 在牛奶里。S类的ABS耐蛋白质降解，可能在呼吸道中具有很高的功能 组织(2，6)。牛奶中几乎所有的SIgA/SIgM都来自粘膜免疫系统，包括呼吸道 因此，我们应该预料到SARS-CoV-2反应的SIgA/Sigm反应，尽管幅度， 这种反应的功能性和持久性仍不得而知。因此，SARS-CoV-2反应性牛奶抗体必须 对其潜在的治疗和保护效果进行全面研究。为了实现这一目标，我们有 招募了1600多名哺乳期参与者，其中包括600多名已从新冠肺炎疾病中康复的人。我们的 使用15个样本的试点数据发现，新冠肺炎后获得的93%的样本含有SARS-CoV-2反应性SIgA抗体。 基于这一早期证据，我们提议的项目打算：(A)测量SARS-CoV-2反应抗体 感染后的牛奶和这种反应的长期持久性；(B)确定中和能力 以及(C)评估这些抗体的非中和、Fc介导的功能。这 综合研究将确定牛奶中的COVID19特异性抗体是否具有保护生物功能和 应该被认为是治疗性抗体的来源。这些数据将为康复期提供一个基础 牛奶抗体的功效研究，并具有超越大流行的影响，服务于填补相对较大的 关于母乳免疫学的知识差距。

项目成果

Safety of breast/chest-feeding by those infected by SARS-CoV-2.

• DOI: 10.1097/mco.0000000000000816
• 发表时间: 2022-03-01
• 期刊: Current opinion in clinical nutrition and metabolic care
• 影响因子: 3.1
• 作者: Powell RLR

In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19.

• DOI: 10.1080/21645515.2024.2303226
• 发表时间: 2024-12-31
• 期刊: Human vaccines & immunotherapeutics
• 影响因子: 4.8

The IgA in milk induced by SARS-CoV-2 infection is comprised of mainly secretory antibody that is neutralizing and highly durable over time.

• DOI: 10.1371/journal.pone.0249723
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Fox A;Marino J;Amanat F;Oguntuyo KY;Hahn-Holbrook J;Lee B;Zolla-Pazner S;Powell RL
• 通讯作者: Powell RL

Qualitative immunoassay for the detection of anti-SARS-COV-2 spike antibody in human milk samples.

• DOI: 10.1016/j.xpro.2022.101203
• 发表时间: 2022-03-18
• 期刊: STAR protocols
• 作者: Yang X;Fox A;Powell RLR
• 通讯作者: Powell RLR

Robust and Specific Secretory IgA Against SARS-CoV-2 Detected in Human Milk.

• DOI: 10.1016/j.isci.2020.101735
• 发表时间: 2020-11-20
• 期刊: iScience
• 影响因子: 5.8
• 作者: Fox A;Marino J;Amanat F;Krammer F;Hahn-Holbrook J;Zolla-Pazner S;Powell RL
• 通讯作者: Powell RL