title: Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.
abstract: BACKGROUND
  Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research.
  
  
  METHODS
  This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose.
  
  
  RESULTS
  619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups.
  
  
  CONCLUSIONS
  Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease.
authors.affiliation: Centro Superior de Investigacion en Salud Publica (CSISP), Valencia, Spain. Electronic address: diez_jav@gva.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Diez-Domingo
authors.forename: Alejandra
authors.initials: A
authors.lastname: Gurtman
authors.forename: Enrique
authors.initials: E
authors.lastname: Bernaola
authors.forename: Francisco
authors.initials: F
authors.lastname: Gimenez-Sanchez
authors.forename: Federico
authors.initials: F
authors.lastname: Martinon-Torres
authors.forename: Valentin
authors.initials: V
authors.lastname: Pineda-Solas
authors.forename: Alfonso
authors.initials: A
authors.lastname: Delgado
authors.forename: Pilar
authors.initials: P
authors.lastname: Infante-Marquez
authors.forename: John Z
authors.initials: JZ
authors.lastname: Liang
authors.forename: Peter C
authors.initials: PC
authors.lastname: Giardina
authors.forename: William C
authors.initials: WC
authors.lastname: Gruber
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Scott
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D013030:Spain; D014611:Vaccination / Q000009:adverse effects / Q000379:methods*
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; C410218:serogroup C meningococcal conjugate vaccine
keywords: 13-Valent pneumococcal conjugate vaccine; 13-valent pneumococcal conjugate vaccine; 50% tissue culture infectious dose; 7-valent pneumococcal conjugate vaccine; AE; CI; CRM(197); ELISA; GMC; GMT; Haemophilus influenzae type b; Hib; IPD; IgG; Immunogenicity; Infants; MMR; MnC; MnC conjugate vaccine using diphtheria toxin cross-reactive material 197; MnCCV-CRM(197); PCV13; PCV7; Pneumococcal vaccination; SAE; SBA; Spain; TCID(50); adverse event; confidence interval; cross-reactive material 197 (nontoxic mutant form of diphtheria toxin); e-diary; electronic diary; enzyme-linked immunosorbent assay; geometric mean concentration; geometric mean titer; immunoglobulin G; invasive pneumococcal disease; measles, mumps, rubella (vaccine); meningococcal group C; serious adverse event; serum bactericidal assay