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.

项目总结