title: Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine.
abstract: We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM(197) plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (> or = 1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (> or = 0.15 microg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules.
authors.affiliation: Johannes-Gutenberg-Universität, Langenbeckstr. 1, 55101 Mainz, Germany.
authors.forename: Heinz-J
authors.initials: HJ
authors.lastname: Schmitt
authors.forename: Gudrun
authors.initials: G
authors.lastname: Maechler
authors.forename: Pirmin
authors.initials: P
authors.lastname: Habermehl
authors.forename: Markus
authors.initials: M
authors.lastname: Knuf
authors.forename: Roland
authors.initials: R
authors.lastname: Saenger
authors.forename: Norman
authors.initials: N
authors.lastname: Begg
authors.forename: Dominique
authors.initials: D
authors.lastname: Boutriau
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology* / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D018073:Haemophilus Vaccines; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate