Objectives To study the effect of standard of care therapy on antibody (Ab) response and functionality of Abs following pneumococcal vaccination using 13-valent conjugate vaccine (PCV13) in patients with systemic vasculitis compared to healthy controls.
Methods In total 49 patients with vasculitis (granulomatosis with polyangiitis=21, Churg-Strauss vasculitis=8, giant cell vasculitis=13; Takayasu=4 and other vasculitis=3) and 49 controls were immunized with a single dose (0.5 ml) PCV13 intramuscularly. Vasculitis patients were treated with azathioprine (n=11), cyclophosphamide +prednisolone (n=6), MTX (n=9), prednisolone without DMARD (n=16), rituximab+DMARDs (3); anti-TNF (n=2), mycophenolate mofetil (n=1) and no active treatment (n=1). Only patients with unchanged dose of DMARDs for at least 4 weeks before vaccination were eligible for the study. Blood samples were taken immediately before and 4–6 weeks after vaccination. Standard ELISA was used to determine pre- and post-PCV13 serotype-specific Ab concentrations for serotypes 6B and 23F. The measurement of functional Abs against one of serotypes (23F) was performed using opsonophagocytic (OPA) assay. Proportions of individuals with postvaccination Ab concentrations ≥1.0 μg/mL (i.e. putative protective levels) for both serotypes were determined, and groups were compared using Chi2 test. Proportion of individuals with positive Ab response (i.e. ≥2-fold increase from pre-PCV13 concentrations) for both serotypes was calculated. Geometric mean Ab concentrations (GMCs) were calculated. Pre- and post-PCV13 Ab levels were compared using paired T-test. Controls were younger (mean age 50.6 years vs 61.5 years) at vaccination and a larger proportion were women (63% vs 51%). Mean disease duration in vasculitis patients was 5.2 years.
Results Pre- to post-PCV13 Ab concentrations increased significantly for 6B and 23F in both patient and control groups (p<0.001). Compared to controls, patients with vasculitis had lower pre- and postvaccination Ab levels for serotype 23F (p=0.012 and p=0.033, respectively) and numerically but not statistically significant lower pre- and post-PCV13 levels for 6B (Table). OPA shows significant increase after vaccination in both patients and controls (p<0.001) although this was numerically more pronounced in controls. Patients receiving any DMARD had significantly lower proportion of subjects reaching protective Ab concentrations (≥1.0 μg/mL) for both serotypes (p=0.04) compared to controls. In addition, patients on DMARDs had lower proportion of responders for both serotypes which was most pronounced for azathioprine and rituximab+DMARD. Prednisolone without DMARD was not associated with impaired Ab responses.
Conclusions PCV13 was immunogenic in patients with established vasculitis. Functionality of serotype specific antibodies was confirmed in both patients and controls although the opsonophagocytotic activity was more pronounced in controls. Treatment with DMARDs, mostly azathioprine or rituximab combined with DMARD but not systemic prednisolone lead to impaired antibody response.
Disclosure of Interest None declared