Protective antigen and toxin neutralization antibody patterns in anthrax vaccinees undergoing serial plasmapheresis

Abstract

Recipients of licensed anthrax vaccine (AVA; Biothrax) could serve as a source of hyperimmune plasma and immunoglobulin for therapy and prophylaxis. We measured serum antibodies during serial weekly to biweekly plasmapheresis in 38 individuals previously vaccinated with 4 to 27 doses of AVA. Immunoglobulin G (IgG) to protective antigen (PA) and toxin neutralization assay (TNA) antibody levels were highly correlated (r = 0.86930 and P < 0.0001 for anti-PA concentration versus TNA concentration). Significant decreases in antibody titer and concentration were observed over time when compared for the number of days from the last AVA injection (P < 0.0001 for both anti-PA and TNA concentration) and for the number of days from the first plasmapheresis (P = 0.0007 for anti-PA concentration and P = 0.0025 for TNA concentration). The rate of the decrease in total IgG concentration (half-life [t(1/2)] = 198.90 days after first plasmapheresis) was significantly less than the decrease in anti-PA IgG (t(1/2) = 63.53 days) (P < 0.0001), indicating that the reduction in anti-PA IgG was more likely due to natural decay than plasmapheresis. The time since the last injection and the time after initial plasmapheresis are important elements in considering an optimal schedule for collecting anthrax hyperimmune plasma. Good correlation between IgG to PA and TNA antibodies suggests that the anti-PA enzyme-linked immunosorbent assay can be used as a high-throughput screen for functional immune reactivity in donor plasma units.

FIG. 1.

IgG antibody to B. anthracis PA concentrations in sera from plasma donors. Antibody levels declined significantly over time for days from last AVA vaccination (P < 0.0001) (A) and for days from initial plasmapheresis (P < 0.0007) (B).

FIG. 2.

B. anthracis TNA antibody concentrations in sera from plasma donors. Antibody levels declined significantly over time for days from last AVA vaccination (P < 0.0001) (A) and for days from initial plasmapheresis (P < 0.0001) (B).

FIG. 3.

Comparative rates of decline between IgG antibody to B. anthracis PA concentrations and total IgG antibody concentrations in sera from plasma donors. The rate of decrease in total IgG concentration was significantly less than that for the IgG to PA concentration over the interval from the last AVA injection (P < 0.0001) (A) and over the interval from initial plasmapheresis (P < 0.0001) (B). Regression lines and respective equations are included.

FIG. 4.

Correlations between IgG to B. anthracis PA and TNA antibody titers (A) and concentrations (B). Regression lines and correlation coefficients (R) are included for each plot.