Journal Article Ahead of print
PubMed: 42746633 DOI: 10.1016/j.cpblue.2026.100088
Pre-vaccine sentinel antibodies predict blunted vaccine responses.
Cell Press Blue
Authors: Lusheng Song, Jin G Park, Ji Qiu, Vel Murugan, Seyedmasoud Mousavi, Ching-Wen Hou, D Mitchell Magee, Zhongxue Chen, Yunro Chung, Stacy Williams, Deborah Adam, Bihong Guo, Candyce McDaniel, Toria Trendler, Gabe Rice, Kelly Connard, Bradley Bobbett, Michael Ritchie, Izamar Garcia, Guillermo Sebastian Trivino Soto, Giovanna Caruth, Eleni Katergaris, Kristen Seifert, Veronica Boyle, Heewook Lee, Damodara Rao Mendu, Viviana Simon, Komal Srivastava, Bharat Thyagarajan, Mike Ryan, Elena Kowalsky, Patrick Breads, David Fetterer, Troy Kemp, Ann Khalsa, Lora Nordstrom, Michael D White, Raquel Salgado, Chad M VanDenBerg, Natacha Montalvo, Craig Woods, Rajat Walia, David Carpentieri, Peter Arden, Christine L Kuryla, Anay Patel, Lauren Stiene, Imke Folkerts, Stefani N Thomas, Anne Davidson … and 8 other authors
Affiliations
- Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
- School of Computing and Augmented Intelligence, Arizona State University, Tempe, AZ, USA.
- Biodesign Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
- Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
- Vaccine, Immunity and Cancer Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
- Valleywise Health, Phoenix, AZ, USA.
- Clinical Research Services, Midwestern University, Glendale, AZ, USA.
- Norton Thoracic Institute, St. Joseph's Hospital & Medical Center, Phoenix, AZ, USA.
- Phoenix Children's Hospital, Phoenix, AZ, USA.
- Dept. Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Abstract
Predicting which individuals will mount poor antibody responses before vaccination could improve personalized vaccination strategies. Here, we conducted a national longitudinal study of humoral immune responses to 185 antigens, including SARS-CoV-2 (n = 3), common microbial pathogens (n = 157), and autoantigens (n = 25), in 1,644 immunosuppressed patients and 2,445 healthy individuals before and after COVID-19 vaccination. Although blunted COVID-19 vaccine responses were more frequent in solid organ transplant recipients and individuals with multiple myeloma, autoimmune disease, inflammatory bowel disease, and human immunodeficiency virus, responses were highly heterogeneous within every cohort, and approximately 5-6% of healthy individuals also mounted weak responses. Pre-existing antibodies to common microbes, including Staphylococcus aureus, respiratory syncytial virus, and human respirovirus 3, consistently predicted post-vaccination antibody responses in both healthy and immunosuppressed populations. These broadly prevalent antimicrobial antibodies represent sentinel antibodies that may serve as biomarkers of system-level humoral immune competence. Using global antimicrobial antibody profiles, we developed a deep-learning predictive model that stratified individuals according to their likelihood of mounting blunted vaccine responses. Together, these findings identify pre-existing antimicrobial antibody profiles as scalable biomarkers of humoral immune responsiveness and provide a framework for predicting vaccine responses before immunization.
MeSH
Antibody Formation, Vaccines, Antibodies, Biomarkers, Vaccination, Viruses, Immunosuppression Therapy