Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients
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.
Authors
- Mengyun Hu (ORCID: https://orcid.org/0000-0003-4495-7501)
- Mark R. Nicolls (ORCID: https://orcid.org/0000-0001-9473-7422)
- Mehul S. Suthar (ORCID: https://orcid.org/0000-0002-2686-8380)
- Bali Pulendran (ORCID: https://orcid.org/0000-0001-6517-4333)
- Nadine Rouphael (ORCID: https://orcid.org/0000-0002-2512-7919)
- Matthew Litvack
- Zhuoqing Fang (ORCID: https://orcid.org/0000-0002-7418-1313)
- Prabhu S. Arunachalam (ORCID: https://orcid.org/0000-0003-0090-5689)
- Xuhuai Ji (ORCID: https://orcid.org/0000-0002-1768-6403)
- Gundeep Dhillon (ORCID: https://orcid.org/0000-0003-0440-1138)
- Harold Sai-Yin Hui
- Yupeng Feng (ORCID: https://orcid.org/0000-0001-8550-2787)
- Holden T. Maecker (ORCID: https://orcid.org/0000-0003-0795-9946)
- Thomas Hagan (ORCID: https://orcid.org/0000-0002-5254-5251)
- Sangeeta Kowli (ORCID: https://orcid.org/0000-0003-0362-572X)
- Alba Grifoni
- Molly Miranda (ORCID: https://orcid.org/0000-0003-1975-207X)
- A Sette
- Ana Paula B N Oliveira
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- La Jolla Institute for Immunology (US)
- Emory Healthcare (US)
- HOPE Clinic (US)
- Guangzhou Eighth People's Hospital (CN)
- Institute of Infection and Immunity (CA)
- Emory National Primate Research Center
- Guangzhou Medical University (CN)
- Stanford University (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102050
- Citations
- 3
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 4.19