title: A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator of parenteral immunization with a group B meningococcal vaccine.
abstract: Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases. We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine. To test this hypothesis, a randomized placebo (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 immunizations. All 14 volunteers completed the 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 effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels 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 bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine.
authors.affiliation: Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Drabick
authors.forename: D B
authors.initials: DB
authors.lastname: Tang
authors.forename: E E
authors.initials: EE
authors.lastname: Moran
authors.forename: A F
authors.initials: AF
authors.lastname: Trofa
authors.forename: J S
authors.initials: JS
authors.lastname: Foster
authors.forename: W D
authors.initials: WD
authors.lastname: Zollinger
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D002927:Cimetidine / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control; D022401:Meningococcal Vaccines; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D006635:Histamine H2 Antagonists; D022401:Meningococcal Vaccines; D002927:Cimetidine