Metabolomic profiling of maternal plasma identifies inverse associations of acetate and urea with anti-SARS-CoV-2 antibody titers following COVID-19 vaccination during pregnancy

Journal of Molecular Medicine Pub Date : 2024-04-03 DOI:10.1007/s00109-024-02438-4

An-Shine Chao, Chiao-Yun Lin, Meng-Han Chiang, Kuan-Ying Lu, Cheng-Kun Tsai, Kuan-Ju Chen, Chih-Wei Chien, Ting-Shu Wu, Yao-Lung Chang, Angel Chao, Gigin Lin, Chih-Yung Chiu

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Abstract

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using ¹H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers.

Key messages

Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases.
Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea.
Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers.

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母体血浆代谢组学分析发现，孕期接种 COVID-19 疫苗后，乙酸盐和尿素与抗 SARS-CoV-2 抗体滴度呈反向关系

摘要我们对接种 mRNA-1273-SARS-CoV-2 疫苗后抗体滴度不同的孕妇血浆样本进行了全面的代谢组学分析。这项研究涉及 62 名孕妇，她们都是在妊娠满 24 周后接种疫苗的。为了量化接种后的血浆抗体滴度，我们采用了符合世界卫生组织国际标准的结合抗体单位（BAU）。随后，我们将研究参与者分为三个不同的 BAU/mL 类别：高滴度（高于 2000）、中滴度（介于 1000 到 2000 之间）和低滴度（低于 1000）。利用 1H 核磁共振波谱对血浆代谢组进行了分析，并将获得的数据与抗体滴度分类相关联。值得注意的是，在抗 SARS-CoV-2 抗体滴度升高的孕妇中，观察到醋酸盐和尿素的血浆浓度降低。这些化合物与抗体滴度之间也存在明显的负相关。对代谢组学途径的分析表明，抗体滴度与四种不同的氨基酸代谢途径之间存在明显的负相关：(1) 苯丙氨酸、酪氨酸和色氨酸的生物合成；(2) 缬氨酸、亮氨酸和异亮氨酸的生物合成；(3) 苯丙氨酸的代谢；(4) 缬氨酸、亮氨酸和异亮氨酸的降解。此外，酮体的合成和降解途径之间也存在明显的联系。总之，我们发现了妊娠期 COVID-19 mRNA 疫苗引发不同体液反应的不同代谢途径。抗 SARS-CoV-2 抗体滴度与醋酸盐（一种微生物衍生代谢产物）和尿素成反比，氨基酸代谢与 SARS-CoV-2 抗体滴度显著相关。

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Journal of Molecular Medicine

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