Sentinel Antibodies May Identify Patients With Blunted Vaccine Responses

Pre-existing antibody profiles may help identify people likely to mount a blunted response to a new vaccine, according to a national longitudinal study of 4089 participants. In the video above, corresponding author Joshua LaBaer, PhD, executive director of the Biodesign Institute at Arizona State University, reviews the study design and major findings.

Investigators analyzed 8687 serum samples from 2445 healthy participants and 1644 people across 6 immunosuppressed cohorts: HIV, multiple myeloma, solid organ malignancy, inflammatory bowel disease, autoimmune disease, and solid organ transplant. Using a multiplexed in-solution protein array, the team measured antibodies to 185 antigens, including SARS-CoV-2 proteins, other viral and bacterial targets, and autoantigens. The work was conducted through the National Cancer Institute’s Serological Sciences Network, a multi-institutional program created to study immune responses to SARS-CoV-2 infection and vaccination.¹,²

After the initial vaccine series, weak anti-receptor-binding domain responses occurred in 6.2% of healthy participants, compared with 71.6% of solid organ transplant recipients, 48.5% of those with multiple myeloma, 43.0% with inflammatory bowel disease, and 39.0% with autoimmune disease. Responses within every cohort were heterogeneous. After a booster, 95.0% of healthy participants had a high response, and most immunosuppressed participants improved; however, 37.9% of transplant recipients and 17.5% of participants with autoimmune disease still had weak or absent responses.¹

The researchers also found that 103 of 114 seroprevalent antibodies, or 90.4%, changed little over 18 months. Antibody levels against common microbes correlated with subsequent COVID-19 vaccine response, suggesting that a person’s existing humoral profile may carry information about future responsiveness.

The study does not establish a clinical test or prove that these profiles predict infection, hospitalization, or severe disease. Sampling was uneven across cohorts, baseline samples were unavailable for some transplant recipients, and the analysis did not include cellular immunity. For clinicians, the finding is best viewed as proof of concept: clinical category alone did not fully explain who responded well or poorly to vaccination.

References:

1. Song L, Park JG, Qiu J, et al. Pre-vaccine sentinel antibodies predict blunted vaccine responses. Cell Press Blue. 2026;1:100088. doi:10.1016/j.cpblue.2026.100088

2. Figueiredo JC, Merin NM, Hamid O, et al. Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 Epidemiologic Cohort Studies. Open Forum Infect Dis. 2022;9:ofac171. doi:10.1093/ofid/ofac171