Antibody fingerprint may predict vaccine response

Clinical takeaway: Clinical risk factors alone do not reliably identify who will mount a weak vaccine response. Preexisting antibody profiles may eventually provide a more individualized measure of immune readiness.

Clinicians can often identify patients at increased risk for poor vaccine responses based on immunosuppression, but those categories are imprecise: some immunosuppressed patients respond well, while some apparently healthy people do not. A large US study suggests a person’s existing antibody profile may provide another way to gauge how strongly the immune system will respond.

Researchers analyzed 8,687 samples from 4,089 healthy and immunosuppressed participants, measuring antibodies against 185 targets before and after COVID-19 vaccination. Weak responses were more common in several immunosuppressed groups, particularly solid organ transplant recipients, but responses varied substantially within every group. About 5% to 6% of healthy participants also mounted weak responses.

Higher levels of preexisting antibodies against several common microbes, particularly Staphylococcus aureus, RSV, and human respirovirus 3, consistently tracked with stronger vaccine responses. These antibodies remained largely stable over time and may reflect a person’s overall ability to mount an antibody response, rather than directly protecting against SARS-CoV-2.

Using the broader antibody profile along with demographic and clinical information, researchers developed a deep-learning model that could stratify patients by likelihood of a weak vaccine response. Prediction was strongest among healthy participants and less reliable in some immunosuppressed groups, including those with autoimmune disease and solid organ transplants.

The findings raise the possibility of a blood-based measure of immune readiness that could eventually help identify patients who may need additional vaccine doses, closer follow-up, or other protective strategies. Whether the antibody signatures predict responses to vaccines beyond COVID-19 or translate into differences in infection or clinical outcomes remains to be determined.

“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,” said senior author Joshua LaBaer.

Source: Song L, et al. (2026 Aug 20) Cell Press Blue. Pre-vaccine sentinel antibodies predict blunted vaccine responses