title: Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled trial.
abstract: BACKGROUND
  The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority.
  
  
  OBJECTIVE
  To determine the safety and immunogenicity of a combination 9-valent pneumococcal-group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months.
  
  
  METHODS
  Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months.
  
  
  METHODS
  Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine).
  
  
  METHODS
  Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions.
  
  
  RESULTS
  MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] microg/mL vs 3.36 [95% CI, 2.57-4.39] microg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] microg/mL vs 1.47 [95% CI, 1.28-1.69] microg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 microg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group.
  
  
  CONCLUSIONS
  Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.
authors.affiliation: Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, Churchill Hospital, Headington, Oxford, UK. jim.buttery@rch.org.au
authors.forename: Jim P
authors.initials: JP
authors.lastname: Buttery
authors.forename: Anna
authors.initials: A
authors.lastname: Riddell
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
authors.forename: Tracey
authors.initials: T
authors.lastname: Chantler
authors.forename: Laura
authors.initials: L
authors.lastname: Lane
authors.forename: Jane
authors.initials: J
authors.lastname: Bowen-Morris
authors.forename: Linda
authors.initials: L
authors.lastname: Diggle
authors.forename: Rhonwen
authors.initials: R
authors.lastname: Morris
authors.forename: Anthony
authors.initials: A
authors.lastname: Harnden
authors.forename: Steven
authors.initials: S
authors.lastname: Lockhart
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.forename: Keith
authors.initials: K
authors.lastname: Cartwright
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
mesh_terms: D000907:Antibodies, Bacterial / Q000096:biosynthesis; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate
chemical_list: D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D011055:Poliovirus Vaccine, Oral; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate