Hu Mengyun, Oliveira Ana Paula B N, Fang Zhuoqing, Feng Yupeng, Miranda Molly, Kowli Sangeeta, Arunachalam Prabhu S, Vasudevan Gowri, Hui Harold Sai-Yin, Grifoni Alba, Sette Alessandro, Litvack Matthew, Rouphael Nadine, Suthar Mehul S, Ji Xuhuai, Maecker Holden T, Hagan Thomas, Dhillon Gundeep, Nicolls Mark R, Pulendran Bali
Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Cell Rep Med. 2025 Apr 15;6(4):102050. doi: 10.1016/j.xcrm.2025.102050. Epub 2025 Apr 4.
The effectiveness of COVID-19 mRNA vaccines is diminished in organ transplant patients. Using a multi-omics approach, we investigate the immunological state of lung transplant (LTX) recipients at baseline and after SARS-CoV-2 mRNA vaccination compared to healthy controls (HCs). LTX patients exhibit a baseline immune profile resembling severe COVID-19 and sepsis, characterized by elevated pro-inflammatory cytokines (e.g., EN-RAGE [also known as S100A12], interleukin [IL]-6), reduced human leukocyte antigen (HLA)-DR expression on monocytes and dendritic cells, impaired cytokine production, and increased plasma microbial products. Single-cell RNA sequencing identifies an enriched monocyte cluster in LTX patients marked by high S100A family expression and reduced cytokine and antigen presentation genes. Post vaccination, LTX patients show diminished antibody, B cell, and T cell responses, along with blunted innate immune signatures. Integrative analysis links these altered baseline immunological features to impaired vaccine responses. These findings provide critical insights into the immunosuppressed condition of LTX recipients and their reduced vaccine-induced adaptive and innate immune responses.
新冠病毒信使核糖核酸（mRNA）疫苗在器官移植患者中的有效性会降低。我们采用多组学方法，研究了肺移植（LTX）受者在基线时以及接种新冠病毒mRNA疫苗后的免疫状态，并与健康对照者（HCs）进行比较。LTX患者的基线免疫特征类似于重症新冠病毒感染和脓毒症，其特征为促炎细胞因子（如EN-RAGE[也称为S100A12]、白细胞介素[IL]-6）水平升高，单核细胞和树突状细胞上人类白细胞抗原（HLA）-DR表达降低，细胞因子产生受损，以及血浆微生物产物增加。单细胞RNA测序确定了LTX患者中一个富集的单核细胞簇，其特征是S100A家族高表达以及细胞因子和抗原呈递基因减少。接种疫苗后，LTX患者的抗体、B细胞和T细胞反应减弱，同时固有免疫信号也减弱。综合分析将这些改变的基线免疫特征与受损的疫苗反应联系起来。这些发现为LTX受者的免疫抑制状况及其疫苗诱导的适应性和固有免疫反应降低提供了关键见解。
