Durable antibody and effector memory T cell responses in breastmilk from women with SARS-CoV-2.

Durable antibody and effector memory T cell responses in breastmilk from women with SARS-CoV-2.
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DOI:
10.3389/fimmu.2022.985226
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发表时间:
2022
影响因子:
7.3
通讯作者:
Arcaro, Kathleen F.
Arcaro, Kathleen F.
中科院分区:
医学2区
文献类型:
--
作者:
Narayanaswamy, Vignesh;Pentecost, Brian T.;Telfer, Janice C.;Burnside, Amy S.;Schneider, Sallie S.;Alfandari, Dominique;Baker, Ryan L.;Saiju, Aman;Nodiff, Sam;Arcaro, Kathleen F.

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鉴于只有25%的孕妇选择接种COVID-19疫苗,母体SARS-CoV-2感染仍然是为未接种疫苗的母亲母乳喂养的婴儿提供保护性被动免疫的重要途径。我们在2020年12月至2021年3月期间招募了30名哺乳期参与者,他们在过去21天内首次出现COVID-19症状并进行了PCR检测。要求参与者在35天内的12个时间点(约每3天)提供连续的双侧乳汁样本。第二组样本在第一组样本开始后至少四个月收集。参与者还被要求提供他们的干血斑和婴儿粪便样本。检测所有样本的受体结合域(RBD)特异性免疫球蛋白(IG)A、IgG和IgM。评估了牛奶样本对刺突蛋白和四种SARS-CoV-2变体的中和能力:D 614 G,Alpha(B.1.1.7),Beta(B.1.351)和Gamma(P.1)。通过测量乳汁中的钠钾离子(Na:K)来评估乳腺上皮的渗透性。使用流式细胞术,在第一次母乳捐赠后35天和至少4个月时表达的乳汁细胞中测定记忆性CD 4和CD 8 T细胞(CD 45 RO+和CCR 7 +/-)以及粘膜归巢性CD 4和CD 8 T细胞(CD 103+)。来自SARS-CoV-2阳性参与者的牛奶抗体中和了刺突复合物。分别有73%、90%和53%的参与者的牛奶对RBD特异性伊加、IgG和IgM具有结合反应性。与显示IgG水平升高但不显示伊加或IgM水平升高的血斑相反,牛奶中的COVID-19反应与强烈的伊加反应相关。27%的参与者乳腺上皮渗透性增加,如Na:K ≥ 0.6所示。≥120日龄的乳汁中CD 45 RO + CCR 7-效应记忆T细胞的百分比显著高于35日龄的乳汁(P< 0.05)。最近感染SARS-CoV-2的参与者和康复者的牛奶中的抗体可以中和尖峰复合物。我们首次发现母乳T细胞富含粘膜记忆T细胞,进一步强调了母乳对婴儿SARS-CoV-2的被动保护作用。
Given that only 25% of pregnant women elect to receive a COVID-19 vaccine, maternal SARS-CoV-2 infection remains an important route of conferring protective passive immunity to breastfed infants of mothers who are not vaccinated. We enrolled 30 lactating participants between December 2020 and March 2021 who had a positive PCR-test and their first COVID-19 symptoms within the previous 21 days. Participants were asked to provide serial bilateral milk samples at 12 timepoints (~ every 3 days) over a period of 35 days. A second set of samples was collected at least four months after the beginning of the first set. Participants also were asked to provide their dried blood spots and infant stool samples. All samples were tested for receptor-binding domain (RBD)-specific immunoglobulin (Ig)A, IgG, and IgM. Milk samples were assessed for neutralizing ability against the spike protein and four SARS-CoV-2 variants: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Permeability of the breast epithelium was assessed by measuring the sodium to potassium ions (Na:K) in milk. Using flow cytometry, memory CD4 and CD8 T cells (CD45RO+ and CCR7+/-) and mucosal-homing CD4 and CD8 T cells (CD103+) were determined in cells from milk expressed at 35 days and at least 4 months after their first milk donation. Milk antibodies from SARS-CoV-2 positive participants neutralized the spike complex. Milk from 73, 90, and 53% of participants had binding reactivities to RBD-specific IgA, IgG, and IgM, respectively. In contrast to blood spots, which showed increased levels of IgG, but not IgA or IgM, the COVID-19 response in milk was associated with a robust IgA response. Twenty-seven percent of participants had increased breast-epithelium permeability, as indicated by Na:K ≥ 0.6. The percentage of CD45RO+CCR7- effector-memory T cells in the day ≥120 milk samples was significantly higher than day 35 samples (P< 0.05). Antibodies in milk from participants with recent SARS-CoV-2 infection and those who recovered can neutralize the spike complex. For the first time we show that breastmilk T cells are enriched for mucosal memory T cells, further emphasizing the passive protection against SARS-CoV-2 conferred to infants via breastmilk.
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发表时间: 2016-09-15
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