Dose-response effects in immunizations with keyhole limpet haemocyanin and rabies vaccine: shift in some immunodeficiency states

We investigated the primary antibody response to the antigens keyhole limpet haemocyanin (KLH) and rabies vaccine (RV). Eighty-one healthy volunteers were injected with nine doses of KLH (ranging from 10 to 2500 micrograms) and 66 volunteers with six doses of RV (ranging from 17 to 680 micrograms protein). Anti-KLH and anti-RV antibodies were determined by ELISA and immunofluorescence (IF) immediately before and 14 days after primary immunization. On the basis of the dose-response curves, optimal and supra-optimal antigen doses were chosen for the assessment of humoral immunocompetence in two groups of patients with uraemic disease, who were treated either by chronic intermittent (hospital) haemodialysis (HD) (n = 16), or continuous ambulatory peritoneal dialysis (CAPD) (n = 23). The patients were randomly immunized with 250 micrograms or 2.5 mg KLH and 170 micrograms or 680 micrograms RV and their antibody responses were compared with those obtained in healthy individuals. We found a definite deficiency in the primary response in haemodialysis patients after challenging with a suitable antigen dose. However, the differences in response rate between patients and controls tended to disappear upon stimulation with a supra-optimal antigen dose. This might indicate that the dose-response curve of a particular antigen is shifted towards higher doses of antigen in immunodeficiency states, which could have important consequences for the testing of immunocompromised patients.