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人乳中针对 SARS-CoV-2 刺突的分泌型 IgA 反应具有高度持久性和中和作用,至少在感染后 1 年的哺乳期内有效。

The Secretory IgA Response in Human Milk Against the SARS-CoV-2 Spike Is Highly Durable and Neutralizing for At Least 1 Year of Lactation Postinfection.

机构信息

Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

出版信息

Breastfeed Med. 2023 Aug;18(8):602-611. doi: 10.1089/bfm.2023.0117.

Abstract

Although in the early pandemic period COVID-19 pathology among young children and infants was typically less severe compared with that observed among adults, this has not remained entirely consistent as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged. There is an enormous body of evidence demonstrating the benefits of human milk antibodies (Abs) in protecting infants against a wide range of enteric and respiratory infections. It is highly plausible that the same holds true for protection against SARS-CoV-2 as this virus infects cells of the gastrointestinal and respiratory mucosae. Understanding the durability of a human milk Ab response over time after infection is critical. Previously, we examined the Abs present in milk of those recently infected with SARS-CoV-2 and concluded that the response was secretory immunoglobulin A (sIgA) dominant and that these titers were highly correlated with neutralization potency. The present study aimed to monitor the durability of the SARS-CoV-2 IgA and secretory Ab (sAb) response in milk from COVID-19-recovered lactating individuals over 12 months in the absence of vaccination or reinfection. This analysis revealed a robust and durable spike-specific milk sIgA response, and at 9-12 months after infection, 88% of the samples exhibited titers above the positive cutoff for IgA and 94% were above the cutoff for sAb. Fifty percent of participants exhibited less than twofold reduction of spike-specific IgA through 12 months. A strong, significant positive correlation between IgA and sAb against spike persisted throughout the study period. Nucleocapsid-specific Abs were also assessed, which revealed significant background or cross-reactivity of milk IgA against this immunogen, as well as limited/inconsistent durability compared with Spike titers. These data suggest that lactating individuals are likely to continue producing spike-specific Abs in their milk for 1 year or more, which may provide critical passive immunity to infants against SARS-CoV-2 throughout the lactation period.

摘要

尽管在新冠疫情早期,与成年人相比,儿童和婴儿的 COVID-19 病理通常较轻,但随着严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)变体的出现,这种情况并非完全一致。有大量证据表明,人乳抗体(Abs)在保护婴儿免受广泛的肠道和呼吸道感染方面具有益处。由于这种病毒感染胃肠道和呼吸道黏膜细胞,因此很有可能对 SARS-CoV-2 也具有保护作用。了解感染后人乳 Ab 反应的持久性至关重要。

此前,我们研究了最近感染 SARS-CoV-2 的人乳中存在的 Abs,并得出结论,该反应以分泌型免疫球蛋白 A(sIgA)为主,且这些滴度与中和效力高度相关。本研究旨在监测 COVID-19 康复哺乳期个体在没有接种疫苗或再次感染的情况下,12 个月内人乳中 SARS-CoV-2 IgA 和分泌型 Ab(sAb)反应的持久性。

该分析揭示了一种强大而持久的刺突特异性乳 sIgA 反应,在感染后 9-12 个月,88%的样本 IgA 滴度高于阳性 cutoff,94%的样本 sAb 滴度高于 cutoff。50%的参与者在 12 个月内刺突特异性 IgA 减少不到两倍。在整个研究期间,IgA 和 sAb 与刺突之间保持着强烈的正相关。还评估了核衣壳特异性 Abs,结果显示,乳 IgA 对该免疫原具有显著的背景或交叉反应性,且与 Spike 滴度相比,其持久性有限或不一致。

这些数据表明,哺乳期个体很可能在 1 年或更长时间内继续在其乳中产生刺突特异性 Abs,这可能在整个哺乳期为婴儿提供针对 SARS-CoV-2 的关键被动免疫。

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