Systems vaccinology identifies clinical and immunological correlates of SARS-CoV-2 vaccine response in solid-organ transplant recipients

Nicolas Gemander, Julika Neumann, Rafael Veiga, Isabelle Etienne, Teresa Prezzemolo, Delphine Kemlin, Pieter Pannus, Stéphanie Depickère, Véronique Olislagers, Inès Vu Duc, Alexandra Waegemans, Margaux Gerbaux, Leoni Bücken, Hafid Dahma, Charlotte Martin, Nicolas Dauby, Maria E Goossens, Isabelle Desombere, Carlos P Roca, Mathijs Willemsen, Stanislas Goriely, Alain Le Moine, Arnaud Marchant, Adrian Liston, Stephanie Humblet-Baron
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Abstract

Solid organ transplant (SOT) recipients are at enhanced risk of adverse outcomes following infectious challenges due to immunosuppressive treatment and additional comorbidities. Unfortunately, SOT recipients are also poor responders to the key medical intervention to preventing infection: vaccines. Here we performed a systems vaccinology study on a cohort of 59 kidney transplant recipients and 31 lung transplant recipients who received the mRNA Pfizer-BioNTech COVID-19 vaccine. Analyzing the immunological status of the patients prior to vaccination, we were able to identify multiple immunological associates of relatively improved vaccine responses following two or three doses of mRNA-based SARS-CoV-2 vaccine. These immunological associates predicted, with 95.0% and 93.3% accuracy, vaccine response after the second and third dose, respectively. Comparison of the immunological associates with vaccine response in SOT recipients revealed two distinct immune configurations: a non-classical configuration, distinct from the immune state of healthy subjects, associated with responses to two doses of mRNA vaccine and that could be mediated partly by the presence of double negative B cell subsets which are more prominently represented in responsive SOT recipients, and a “normalized” configuration, closer to the immune state of healthy subjects, associated with potent antibody responses to three doses of mRNA vaccine. These results suggest that immunosuppression in SOT recipients can result in distinct immune states associated with different trade-offs in vaccine responsiveness. Immune phenotyping of SOT recipients for immune constellation may be an effective approach for identifying patients most at risk of poor vaccine responses and susceptibility to vaccine-preventable diseases.
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系统疫苗学确定了实体器官移植受者对 SARS-CoV-2 疫苗反应的临床和免疫学相关性
由于免疫抑制治疗和额外的合并症,实体器官移植(SOT)受者在面临感染挑战后出现不良后果的风险更高。不幸的是,SOT 受者对预防感染的关键医疗干预措施--疫苗的反应也很差。在此,我们对接受了辉瑞-生物技术公司 COVID-19 mRNA 疫苗的 59 例肾移植受者和 31 例肺移植受者进行了系统疫苗学研究。通过分析接种疫苗前患者的免疫状态,我们发现了接种两到三剂基于 mRNA 的 SARS-CoV-2 疫苗后疫苗应答相对改善的多种免疫学关联。这些免疫相关因子预测第二剂和第三剂疫苗反应的准确率分别为 95.0% 和 93.3%。将这些免疫学相关因素与 SOT 受试者的疫苗反应进行比较,发现了两种不同的免疫结构:一种是非经典结构,与健康受试者的免疫状态不同,与对两剂 mRNA 疫苗的反应有关,部分原因可能是双阴性 B 细胞亚群的存在,这种亚群在有反应的 SOT 受试者中表现得更为突出;另一种是 "正常化 "结构,更接近健康受试者的免疫状态,与对三剂 mRNA 疫苗的强效抗体反应有关。这些结果表明,SOT 受体的免疫抑制可导致不同的免疫状态,与疫苗应答性的不同权衡有关。对 SOT 受试者的免疫表型进行分析以确定其免疫状态,可能是一种有效的方法,可用于识别疫苗应答不良和易患疫苗可预防疾病的高危患者。
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