A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ORAL CIMETIDINE AS AN IMMUNOPOTENTIATOR OF PARENTERAL IMMUNIZATION WITH A GROUP-B MENINGOCOCCAL VACCINE

Cimetidine (CIM) is an H2-receptor antagonist with a long history of c linical rue in peptic ulcer disease. In addition to its inhibitory eff ect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. C IM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of ch ronic infectious and neoplastic diseases. We postulated that orally ad ministered CIM, like an adjuvant, could augment the immunologic respon se to a parenteral vaccine. To test this hypothesis, a radomized place bo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart. Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two in immunizations All 14 volunteers completed t he study with excellent compliance. Sera were tested for anti-OMP and bactericidal antibodies. The groups were comparable in terms of gender distribution age and baseline anti-OMP titers. Reactogenicity to the vaccine was mild and comparable between groups. There was little effec t of CIM (over PLB) on anti-OMP or functional bactericidal antibody le vels over time. Geometric means of maximum OMP antibody, increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in b actericidal antibody level compared to 2.2 for PLB (CI. 1.4-3.4). We c onclude that oral CIM was not effective as an immunopotentiator of imm unization with this group B meningococcal vaccine. (C) 1997 Elsevier S cience Ltd.