Here, we characterize the immune response to COVID-19 vaccines in a large longitudinal cohort of IDP with a wide spectrum of immune disorders and healthy volunteers (HVs; the control group) by measuring postvaccination antibody concentrations, percent angiotensin-converting enzyme 2 (ACE2) inhibition (pseudo-neutralization capacity) against variants of concern, breakthrough infections, and vaccine-related adverse events from prevaccination up to 6 months after dose 3. Here, ACE2 is linked to COVID-19.