SARS-CoV-2 vaccine failure rates and predictors of immune response in a diverse immunocompromised patient population.

Publication date: Jul 12, 2025

Determining individual responses to vaccination is critical for effective prevention of SARS-CoV-2 infection, particularly in populations at risk of vaccine failure. In this prospective study, we collected serum specimens prior to the first and post-second and -third vaccinations to examine the quantity, quality, and durability of immune responses to SARS-CoV-2 vaccination in patients receiving various immune-modulating therapies. To determine rates of vaccine failure, we measured SARS-CoV-2 anti-spike protein immunoglobulin G and neutralisation titres. We analysed post-vaccination serum samples from 293 potentially immunocompromised patients (10.2 % haematologic malignancies, 56.0 % solid tumours, 27.6 % neuroimmunological conditions, and 6.1 % other). Based on IgG titres, 22.4 % and 12.0 % of cases were deemed vaccine failures by serology within 6 months of the second and third COVID-19 vaccinations, respectively; these rates were 32.7 % and 13.9 %, respectively, based on neutralisation. Notably, 12.2 % of samples did not have functional neutralising antibodies despite positive serology (mismatched result) within 6 months of the second COVID-19 vaccine dose. The highest rate of vaccine failure occurred in patients receiving active B-cell depleting therapies (primarily haematological malignancies or neuroimmunological conditions); those receiving cytotoxic chemotherapy or immune checkpoint inhibitors (predominantly patients with solid tumours) were at the lowest risk for vaccine failure. Among patients receiving potentially immunosuppressive therapies, individuals treated with B-cell depletion therapies have high risk for vaccine failure after COVID-19 vaccination, but the rate of failure declines significantly with subsequent doses. In these populations, positive serology tests alone may not signify a protective immune response. Supported by a grant from Regeneron Pharmaceuticals, Inc. , and P54 CA260560.

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