title: Safety and immunogenicity of pneumococcal conjugate vaccine in combination with diphtheria, tetanus toxoid, pertussis and Haemophilus influenzae type b conjugate vaccine.
abstract: BACKGROUND
  Pneumococcal polysaccharide/protein conjugate vaccines (PnCV) are immunogenic and effective in infancy. However, an addition to the nine currently recommended vaccine injections during the first year of life of African children may be a deterrent to participation in a PnCV program. Thus we have evaluated the safety and immunogenicity of a 9-valent PnCV (Wyeth Lederle Pediatrics and Vaccines) mixed with diphtheria, tetanus toxoid, cell pertussis and type b (TETRAMUNE).
  
  
  METHODS
  Healthy Gambian infants were randomized at the age of 2 months to receive three doses 1 month apart of either (1) placebo reconstituted in TETRAMUNE in the right thigh (control) or (2) PnCV in the left thigh and TETRAMUNE in the right thigh (separate) or (3) PnCV reconstituted in TETRAMUNE as a single injection in the right thigh (combined). The vaccines were given together with routine Expanded Program on Immunization vaccines. Adverse reactions were recorded after vaccination, and antibody concentrations were measured by enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Local induration and tenderness were observed more commonly at the site of injection of TETRAMUNE than at the site of injection with PnCV after each dose of vaccination. Swelling at the site of injection was encountered more frequently at the site of administration of TETRAMUNE than at the site of administration PnCV ( P< 0.00001 for Doses 1 and 2 and P< 0.0009 for Dose 3). Swelling at the site of administration of TETRAMUNE mixed with PnCV was comparable with that observed for TETRAMUNE alone. Although most mothers reported that the babies "felt hot" 24 h after each injection, febrile reactions (temperature, >or=38 degrees C) were infrequent and resolved with antipyretics. Geometric mean titer for anti-polyribosylribitol phosphate antibody was 11.6 microg/ml [95% confidence limits (95% CI), 9.2, 14.6] in the control group and comparable with 13.3 microg/ml (95% CI 11.0, 16.0) in the combined group and significantly higher at 17.9 microg/ml (95% CI 14.7, 21.9; P= 0.01) in the separate group. Geometric mean concentrations of serotype-specific pneumococcal antibodies were higher in the combined group than the separate group for all nine serotypes. Antibody responses to diphtheria and pertussis antigens were similar in all groups. Anti-tetanus toxoid antibody concentrations were lowest in the combined group (6.66 IU/ml, 95% CI 5.77, 7.68 in the control group; 5.15 IU/ml, 95% CI 4.39, 6.03 in the combined group; P= 0.02). However, all vaccinees achieved protective antibody values.
  
  
  CONCLUSIONS
  The combination of TETRAMUNE and PnCV is safe and immunogenic.
authors.affiliation: Imperial College School of Medicine, London, United Kingdom.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Obaro
authors.forename: Godwin C
authors.initials: GC
authors.lastname: Enwere
authors.forename: Maria
authors.initials: M
authors.lastname: Deloria
authors.forename: Shabbar
authors.initials: S
authors.lastname: Jaffar
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.forename: Kate
authors.initials: K
authors.lastname: Brainsby
authors.forename: Hans
authors.initials: H
authors.lastname: Hallander
authors.forename: Pamela
authors.initials: P
authors.lastname: McInnes
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: Keith P W J
authors.initials: KP
authors.lastname: McAdam
mesh_terms: D016667:Bacterial Capsules; D016001:Confidence Intervals; D003906:Developing Countries; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage*; D005260:Female; D005714:Gambia; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D006801:Humans; D007109:Immunity / Q000502:physiology*; D017589:Immunization Programs / Q000458:organization & administration; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D011336:Probability; D012016:Reference Values; D012449:Safety; D014611:Vaccination / Q000379:methods*; D017778:Vaccines, Combined / Q000008:administration & dosage; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C080881:diphtheria-tetanus-pertussis-haemophilus b conjugate vaccine