<b>Immuno-microbial signature of vaccine-induced immunity of</b> <b> </b><b>SARS-CoV-2</b>

Although vaccines address critical public health needs, inter-individual differences in re- 14 sponses are not always considered in their development. Determining vaccine effectiveness on an 15 individual basis is a concern in outbreak response and disease control. In this pilot study, pre- and 16 post- antiviral, immunological, and gut microbiota responses were characterized to examine the 17 effectiveness of the SARS-CoV-2 mRNA inoculation. Blood and stool samples were collected before 18 administration of the biological products and at 2-to-4-week intervals after the administration of the 19 first dose. A cohort of 14 adults were separated into two groups based on the neutralizing antibody 20 levels after 10 weeks of inoculation: high neutralization (HN) and low neutralization (LN). Bivariate 21correlation analysis was performed to examine associations between gut microbiota, inflammation 22 response and neutralization capacity at 10-weeks post-vaccination. This analysis between the two 23 groups indicates significant differences in gut microbiota composition and inflammatory factors 24 with significant correlations between bacterial species found at higher abundance in the HN group 25 being negatively correlated to a panel of inflammation factors. There was also a significant inverse 26 relationship (R=-0.5, p=0.03) between HMGB-1 plasma concentrations pre-vaccination and neutral- 27 ization capacity at 10 weeks post inoculation period. Altogether, our results implicate that HMGB- 28 1 is a potential biomarker in predicting SARS-CoV-2 mRNA vaccine effectiveness.尽管疫苗可满足关键公共卫生需求，但疫苗研发过程中往往未充分考量个体间的应答差异。基于个体层面评估疫苗有效性，是疫情应对与疾病防控领域的核心关切。本预实验研究对受试者接种前后的抗病毒应答、免疫应答与肠道菌群应答进行了表征，以评估严重急性呼吸综合征冠状病毒2（SARS-CoV-2）mRNA疫苗的接种效果。在接种该生物制剂前，以及首剂接种后每2至4周的时间点采集血液与粪便样本。本队列共纳入14名成人受试者，于接种10周后根据中和抗体水平分为两组：高中和组（HN）与低中和组（LN）。本研究采用双变量相关分析，探究接种10周后肠道菌群、炎症应答与中和能力之间的关联。两组间的对比分析显示，肠道菌群组成与炎症因子水平存在显著差异；高中和组中丰度更高的细菌类群与一系列炎症因子呈显著负相关。接种前血浆高迁移率族蛋白B1（HMGB-1）浓度与接种10周后的中和能力之间，也存在显著负相关关系（R=-0.5，p=0.03）。综上，本研究结果表明，HMGB-1可作为预测SARS-CoV-2 mRNA疫苗有效性的潜在生物标志物。