title: Glycoconjugate vaccines and immune interactions, and implications for vaccination schedules.
abstract: Conjugate vaccines using diphtheria toxoid variant (CRM(197)), diphtheria toxoid and tetanus toxoid (TT) as carrier protein may induce immune interactions (interference or impairment as measured by lower antibody levels, or enhancement [higher antibody levels]) when coadministered with other vaccines. Immune enhancement occurs when two TT conjugates are coadministered. CRM(197) conjugate vaccines induce immune bystander interference when given with diphtheria-tetanus-acellular pertussis vaccines, which reduces responses to coadministered Haemophilus influenzae type b vaccine conjugated to TT. These bystander effects are greater as the amount of CRM(197) administered increases. When large amounts of either TT or CRM(197) are coadministered, dose-related carrier-induced epitopic suppression may occur, affecting immune responses to meningococcal or pneumococcal polysaccharides. These observations have implications for vaccine scheduling. The range of available alternative vaccines means that specific vaccine coadministrations can avoid or reduce CRM(197)-induced interference. Potential interactions arising from new CRM(197) or TT conjugates will need to be thoroughly examined.
authors: Health Protection Agency, Clinical Sciences Building 2, PO Box 209, Manchester Royal Infirmary, Manchester, M13 9WZ, UK. ray.borrow@hpa.org.uk
authors: Ray
authors: R
authors: Borrow
authors: Ron
authors: R
authors: Dagan
authors: Fred
authors: F
authors: Zepp
authors: Hans
authors: H
authors: Hallander
authors: Jan
authors: J
authors: Poolman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000737:chemistry; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004347:Drug Interactions; D006801:Humans; D007115:Immunization Schedule; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000737:chemistry; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D004168:Diphtheria Toxoid; D004337:Drug Carriers; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin)