title: Safety and immunogenicity of CRM197-conjugated pneumococcal-meningococcal C combination vaccine (9vPnC-MnCC) whether given in two or three primary doses.
abstract: This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal-meningococcal conjugate vaccine in two doses vs. three doses. Infants (N=223) received 9vPnC-MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC-MnCC or 23-valent pneumococcal-polysaccharide vaccine (23vPPS) and CRM197-MnCC, at 12 months. Safety was monitored and IgG measured at 3, 6, 12 and 13 months in all subjects and serum bactericidal activity (SBA) in half. The 9vPnC-MnCC vaccine was safe and induced significant IgG to all components. Three doses induced higher antibody GMCs (geometric mean concentrations) at 6 months to seven of nine pneumococcal serotypes. This was most significant for 6B and 23F (p<0.001), that also showed lower rate of responders>0.35 (6B, 23F) and >0.5 microg/mL (6B). Antibody GMCs remained lower following 9vPnC-MnCC booster in subjects primed with two doses although only significant for serotype 18C. Significant memory responses were observed 1 week after the 23vPPS toddler dose. MnCC-IgG GMC was lower after two doses, however with comparable SBA. This study shows that the 9vPnC-MnCC vaccine is safe and induces successful immunological memory, whether given in two or three primary doses.
authors.affiliation: Department of Immunology, Landspitali University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. veiga@lsh.is
authors.forename: Sigurveig Th
authors.initials: ST
authors.lastname: Sigurdardottir
authors.forename: Katrin
authors.initials: K
authors.lastname: Davidsdottir
authors.forename: Vilhjalmur A
authors.initials: VA
authors.lastname: Arason
authors.forename: Olof
authors.initials: O
authors.lastname: Jonsdottir
authors.forename: France
authors.initials: F
authors.lastname: Laudat
authors.forename: William C
authors.initials: WC
authors.lastname: Gruber
authors.forename: Ingileif
authors.initials: I
authors.lastname: Jonsdottir
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D050296:Microbial Viability; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D017778:Vaccines, Combined; C410218:serogroup C meningococcal conjugate vaccine; C028581:CRM197 (non-toxic variant of diphtheria toxin)