de Graaf Sebastiaan C, Bondt Albert, van Rijswijck Danique M H, Juncker Hannah G, Mulleners Sien J, Damen Mirjam J A, Hoek Max, van Keulen Britt J, van Goudoever Johannes B, Heck Albert J R, Dingess Kelly A
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, Netherlands.
Netherlands Proteomics Center, Utrecht, Netherlands.
Front Nutr. 2024 Jan 15;10:1305086. doi: 10.3389/fnut.2023.1305086. eCollection 2023.
INTRODUCTION: Upon vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humans will start to produce antibodies targeting virus specific antigens that will end up in circulation. In lactating women such antibodies will also end up in breastmilk, primarily in the form of secretory immunoglobulin A1 (SIgA1), the most abundant immunoglobulin (Ig) in human milk. Here we set out to investigate the SIgA1 clonal repertoire response to repeated SARS-CoV-2 vaccination, using a LC-MS fragment antigen-binding (Fab) clonal profiling approach. METHODS: We analyzed the breastmilk of six donors from a larger cohort of 109 lactating mothers who received one of three commonly used SARS-CoV-2 vaccines. We quantitatively monitored the SIgA1 Fab clonal profile over 16 timepoints, from just prior to the first vaccination until 15 days after the second vaccination. RESULTS: In all donors, we detected a population of 89-191 vaccine induced clones. These populations were unique to each donor and heterogeneous with respect to individual clonal concentrations, total clonal titer, and population size. The vaccine induced clones were dominated by persistent clones (68%) which came up after the first vaccination and were retained or reoccurred after the second vaccination. However, we also observe transient SIgA1 clones (16%) which dissipated before the second vaccination, and vaccine induced clones which uniquely emerged only after the second vaccination (16%). These distinct populations were observed in all analyzed donors, regardless of the administered vaccine. DISCUSSION: Our findings suggest that while individual donors have highly unique human milk SIgA1 clonal profiles and a highly personalized SIgA1 response to SARS-CoV-2 vaccination, there are also commonalities in vaccine induced responses.
引言：接种针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的疫苗后，人体将开始产生针对病毒特异性抗原的抗体，这些抗体最终会进入循环系统。在哺乳期妇女中，此类抗体会以分泌型免疫球蛋白A1（SIgA1）的形式进入母乳，SIgA1是母乳中最丰富的免疫球蛋白（Ig）。在此，我们采用液相色谱-质谱片段抗原结合（Fab）克隆分析方法，研究反复接种SARS-CoV-2疫苗后SIgA1克隆库的反应。 方法：我们分析了来自109名接种三种常用SARS-CoV-2疫苗之一的哺乳期母亲的较大队列中的6名捐赠者的母乳。我们在16个时间点定量监测SIgA1 Fab克隆谱，从首次接种前直至第二次接种后15天。 结果：在所有捐赠者中，我们检测到89 - 191个疫苗诱导克隆群体。这些群体对每个捐赠者而言都是独特的，在个体克隆浓度、总克隆滴度和群体大小方面存在异质性。疫苗诱导克隆以持续克隆为主（68%），这些克隆在首次接种后出现，并在第二次接种后保留或再次出现。然而，我们也观察到短暂的SIgA1克隆（16%），它们在第二次接种前消失，以及仅在第二次接种后才独特出现的疫苗诱导克隆（16%）。在所有分析的捐赠者中都观察到了这些不同的群体，无论接种的是哪种疫苗。 讨论：我们的研究结果表明，虽然个体捐赠者的母乳SIgA1克隆谱高度独特，对SARS-CoV-2疫苗的SIgA1反应高度个性化，但疫苗诱导反应也存在共性。
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