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由 SARS-CoV-2 感染引起的牛奶中的 IgA 主要由分泌型抗体组成,这种抗体具有中和作用,并且随着时间的推移具有高度持久性。

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

机构信息

Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

Health Sciences Research Institute, University of California Merced, Merced, California, United States of America.

出版信息

PLoS One. 2022 Mar 9;17(3):e0249723. doi: 10.1371/journal.pone.0249723. eCollection 2022.

Abstract

Approximately 10% of infants infected with SARS-CoV-2 will experience COVID-19 illness requiring advanced care. A potential mechanism to protect this population is passive immunization via the milk of a previously infected person. We and others have reported on the presence of SARS-CoV-2-specific antibodies in human milk. We now report the prevalence of SARS-CoV-2 IgA in the milk of 74 COVID-19-recovered participants, and find that 89% of samples are positive for Spike-specific IgA. In a subset of these samples, 95% exhibited robust IgA activity as determined by endpoint binding titer, with 50% considered high-titer. These IgA-positive samples were also positive for Spike-specific secretory antibody. Levels of IgA antibodies and secretory antibodies were shown to be strongly positively correlated. The secretory IgA response was dominant among the milk samples tested compared to the IgG response, which was present in 75% of samples and found to be of high-titer in only 13% of cases. Our IgA durability analysis using 28 paired samples, obtained 4-6 weeks and 4-10 months after infection, found that all samples exhibited persistently significant Spike-specific IgA, with 43% of donors exhibiting increasing IgA titers over time. Finally, COVID-19 and pre-pandemic control milk samples were tested for the presence of neutralizing antibodies; 6 of 8 COVID-19 samples exhibited neutralization of Spike-pseudotyped VSV (IC50 range, 2.39-89.4ug/mL) compared to 1 of 8 controls. IgA binding and neutralization capacities were found to be strongly positively correlated. These data are highly relevant to public health, not only in terms of the protective capacity of these antibodies for breastfed infants, but also for the potential use of such antibodies as a COVID-19 therapeutic, given that secretory IgA is highly in all mucosal compartments.

摘要

约 10%感染 SARS-CoV-2 的婴儿会出现需要高级护理的 COVID-19 疾病。保护这一人群的一种潜在机制是通过先前感染过的人的乳汁进行被动免疫。我们和其他人已经报告了人乳中存在 SARS-CoV-2 特异性抗体。我们现在报告了 74 名 COVID-19 康复参与者乳汁中 SARS-CoV-2 IgA 的流行情况,发现 89%的样本对 Spike 特异性 IgA 呈阳性。在这些样本的一个亚组中,95%的样本表现出强烈的 IgA 活性,根据终点结合滴度确定,其中 50%被认为是高滴度。这些 IgA 阳性样本也对 Spike 特异性分泌型抗体呈阳性。IgA 抗体和分泌型抗体的水平显示出强烈的正相关。与 IgG 反应相比,在测试的乳汁样本中,分泌型 IgA 反应占主导地位,IgG 反应存在于 75%的样本中,只有 13%的情况下发现 IgG 反应的滴度较高。我们使用 28 对配对样本进行的 IgA 持久性分析,在感染后 4-6 周和 4-10 个月获得,发现所有样本均表现出持续显著的 Spike 特异性 IgA,其中 43%的供体随时间推移表现出 IgA 滴度增加。最后,对 COVID-19 和大流行前对照乳样进行了中和抗体的检测;与 8 个对照中的 1 个相比,8 个 COVID-19 样本中有 6 个显示出对 Spike 假型 VSV 的中和作用(IC50 范围为 2.39-89.4ug/ml)。IgA 结合和中和能力呈强烈正相关。这些数据与公共卫生密切相关,不仅因为这些抗体对母乳喂养婴儿的保护能力,而且因为这些抗体作为 COVID-19 治疗剂的潜在用途,因为分泌型 IgA 在所有黏膜隔室中含量都很高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f07/8906612/77b69b6d7a47/pone.0249723.g001.jpg

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