基线肠道微生物群与三剂BNT162b2后一年的长期免疫反应相关。

Baseline Gut Microbiota Was Associated with Long-Term Immune Response at One Year Following Three Doses of BNT162b2.

作者信息

Zhang Li-Na, Tan Jing-Tong, Ng Ho-Yu, Liao Yun-Shi, Zhang Rui-Qi, Chan Kwok-Hung, Hung Ivan Fan-Ngai, Lam Tommy Tsan-Yuk, Cheung Ka-Shing

机构信息

Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

School of Clinical Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Vaccines (Basel). 2024 Aug 14;12(8):916. doi: 10.3390/vaccines12080916.

DOI:10.3390/vaccines12080916

PMID:39204040

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11359560/

Abstract

BACKGROUND

This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2.

METHODS

Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis.

RESULTS

A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2-59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. (logLDA score = 2.38, = 0.003; relative abundance of 2.97 × 10 vs. 0.03%, = 0.001), (logLDA score = 4.29, = 0.024; relative abundance of 0.14% vs. 2.40%, = 0.014) and (logLDA score = 2.15, = 0.022; relative abundance of 0.01% vs. 0, = 0.010) were enriched in low responders. (logLDA score = 2.99, = 0.048; relative abundance of 0.09% vs. 0.36%, = 0.049) and (logLDA score = 2.38, = 0.014; relative abundance of 1.2 × 10% vs. 0, = 0.044) were enriched in high responders. was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (logLDA score = 2.63), which contributes to inflammation and antibody production. was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (logLDA score = 2.14).

CONCLUSION

Among three-dose BNT162b2 recipients, , and were associated with poorer immunogenicity at one year, while and was associated with a better response.

摘要

背景

本研究探讨接种疫苗后针对新冠病毒的中和IgG抗体水平随时间的下降情况。我们开展了这项前瞻性队列研究，以调查三剂BNT162b2疫苗接种后肠道微生物群在宿主免疫反应中的作用。

方法

从香港的三个中心招募接受三剂BNT162b2疫苗的受试者。在接种第一剂疫苗前及一年时间点采集血样，通过IgG酶联免疫吸附测定法确定中和抗体（NAb）水平。主要结局为高免疫反应（NAb>600 AU/mL）。我们对基线粪便样本进行鸟枪法DNA宏基因组测序，使用线性判别分析效应大小分析来识别与高免疫反应相关的细菌种类和代谢途径。

结果

共招募了125名受试者（中位年龄：52岁[四分位间距：46.2 - 59.0]；男性：43名[34.4%]），在一年时间点有20名被视为低反应者。（对数线性判别分析得分 = 2.38，P = 0.003；相对丰度为2.97×10对比0.03%，P = 0.001）、（对数线性判别分析得分 = 4.29，P = 0.024；相对丰度为0.14%对比2.40%，P = 0.014）和（对数线性判别分析得分 = 2.15，P = 0.022；相对丰度为0.01%对比0，P = 0.010）在低反应者中富集。（对数线性判别分析得分 = 2.99，P = 0.048；相对丰度为0.09%对比0.36%，P = 0.049）和（对数线性判别分析得分 = 2.38，P = 0.014；相对丰度为1.2×10%对比0，P = 0.044）在高反应者中富集。与嘧啶核糖核苷酸从头生物合成的超级途径呈负相关（对数线性判别分析得分 = 2.63），该途径促进炎症和抗体产生。与包括组氨酸、嘌呤和嘧啶生物合成超级途径在内的抗炎过程相关途径呈正相关（对数线性判别分析得分 = 2.14）。