CHIMERIC antigen receptor T cell therapy impact on vaccine immunity has been evaluated in a prospective study, revealing reduced seroprotection against multiple vaccine-preventable pathogens despite stable overall antibody levels.
Humoral immune-related adverse events, including hypogammaglobulinaemia and B cell depletion, are recognised complications following this treatment for haematologic malignancies and may increase long-term infection risk.
The study examined pathogen-specific humoral immunity in 100 individuals receiving therapy targeting CD19 and 28 individuals receiving CD20, which affects B cells, or B cell maturation antigen respectively.
Antibody responses were measured before treatment and up to one year afterwards, covering 12 vaccine-preventable pathogens alongside high-throughput antibody profiling. In addition, 72 participants were assessed for vaccine responses following treatment.
Persistence of Antibody Levels
Findings showed that pathogen-specific humoral immunity did not significantly change following treatment targeting CD19, CD20, or B cell maturation antigen. Despite this apparent stability, clinically relevant gaps in protection were observed.
By one year after treatment, seroprotective antibodies were absent for up to one-third of routine vaccine-preventable pathogens in those receiving CD19 or CD20 targeted therapy.
The effect was more pronounced in individuals receiving therapy directed at plasma cells via B cell maturation antigen, where nearly half of vaccine-preventable pathogens lacked adequate seroprotection.
These findings indicate that while total antibody levels may appear preserved, protective immunity against specific pathogens may be insufficient in a substantial proportion of patients.
Predictors of Vaccine Response
Analysis of vaccine responsiveness identified pre-vaccination B cell count as the primary predictor of effective immune response. Individuals with higher B cell counts prior to vaccination were more likely to mount a protective response following treatment.
These findings highlight an important consideration for clinicians managing patients after chimeric antigen receptor T cell therapy. Although overall antibody profiles may remain stable, significant deficits in protective immunity persist, underscoring the need for careful monitoring and tailored vaccination strategies.
Reference
Ozog S et al. Influence of B cell-lineage targeted CAR-T cell therapy on humoral immunity and vaccine-induced antibody response. Nat Commun. 2026;DOI:10.1038/s41467-026-71473-1.
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