Hidden antibody patterns in your blood may reveal how well your immune system will respond to a vaccine before you get the shot.
Before someone receives a COVID-19 vaccine, their blood may already offer clues to how strongly their immune system will respond. Some of those clues come from antibodies against other microbes, rather than the virus the vaccine is designed to target.
In a study led by Arizona State University, people with higher levels of certain preexisting antibodies tended to respond more strongly to COVID-19 vaccination. These included antibodies against the bacterium Staphylococcus aureus and the respiratory viruses RSV and human respirovirus 3. The findings suggest that previous immune encounters may leave a measurable pattern that helps predict the response to a vaccine.
The researchers call these “sentinel” antibodies. They are not necessarily attacking the vaccine’s target directly. Instead, their presence may indicate how readily the part of the immune system that produces antibodies can respond. The study, published in Cell Press Blue, explored whether these individual clues and broader antibody patterns could help identify people likely to have weak vaccine responses.
Good health doesn’t guarantee strong vaccine responses
Age, sex, genetics, previous illnesses, and underlying health conditions have all been linked to differences in vaccine response. Conditions that compromise the immune system often raise the risk of a weaker response, but a person’s health category does not tell the whole story.
That variation was evident among the study’s 4,089 participants. The group included healthy volunteers and people with conditions or treatments associated with immune suppression, including HIV, multiple myeloma, cancers in solid organs, autoimmune disease, inflammatory bowel disease, and solid organ transplantation. Several immunosuppressed groups were more likely to have reduced responses to COVID-19 vaccination. Yet some immunosuppressed participants responded strongly, while about 5% to 6% of healthy participants had weak responses.
Antibody fingerprints help predict vaccine responses
An antibody profile could potentially capture differences that those broad categories miss. Scientists usually assess vaccine response after vaccination by measuring the antibodies produced against its target. The ASU team and collaborators at medical and research institutions across the country investigated how much they could learn before the shot.
They analyzed 8,687 blood samples collected before and after COVID-19 vaccination, measuring antibodies against 185 antigens, the targets the immune system recognizes. The panel included targets from SARS-CoV-2, the virus that causes COVID-19, other common viruses and bacteria, and targets associated with autoimmune diseases.
Technology that measures many antibody responses at once allowed the team to look beyond a person’s response to any single pathogen. Together, those measurements formed a broad antibody “fingerprint,” reflecting encounters with many different immune targets.
The researchers then used a deep-learning model, a type of artificial intelligence, to examine patterns across the full panel. Rather than relying on a few sentinel antibodies individually, the model combined measurements into a broader immune profile that helped distinguish strong vaccine responders from weak ones. AI allowed the team to search millions of biological data points for subtle predictive relationships.
“What our study found is that certain biomarkers, when analyzed with AI, can predict who is likely to respond well to a vaccine, even before they receive it. This suggests that some people may be more immune-ready than others,” says Joshua LaBaer, who led the study.
LaBaer is executive director of ASU’s Biodesign Institute and director of its Virginia G. Piper Center for Personalized Diagnostics.
Antibody profiles could help tailor vaccination
The approach is among the first to use a broad antibody fingerprint from before vaccination to assess immune readiness. Because it relies on antibody patterns in blood, it may be easier to adapt for clinical use than some prediction methods that require genetic analysis. It could also help researchers understand why vaccine responses differ by examining the wider antibody profile rather than focusing only on antibodies against one disease.
The findings need validation in additional studies and with other vaccines before researchers can establish whether they apply beyond COVID-19. If validated, sentinel antibody profiling could help guide vaccine testing and development, as well as care for people at risk of weak immune responses. Doctors might eventually use it to identify patients who need additional doses, closer follow-up, or other protective measures.
Reference: “Pre-vaccine sentinel antibodies predict blunted vaccine responses” by 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, Thomas Hickey, Nancy Roche, Ligia Pinto, Norman Kleiman, Carlos Cordon-Cardo, Amy B. Karger, Peter Gregersen and Joshua LaBaer, 20 August 2026, Cell Press Blue.
DOI: 10.1016/j.cpblue.2026.100088
This study received funding from NIH/National Institutes of Health, NIH/National Cancer Institute and Autoimmunity Centers of Excellence.
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