title: Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period.
abstract: OBJECTIVE
  To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic.
  
  
  METHODS
  Randomized clinical trial.
  
  
  METHODS
  Suburban New Orleans pediatric population.
  
  
  METHODS
  Convenience sample of 150 healthy infants.
  
  
  METHODS
  Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide.
  
  
  RESULTS
  The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01).
  
  
  CONCLUSIONS
  Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.
authors.affiliation: Department of Pediatrics, Wyler Children's Hospital, University of Chicago, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Miller
authors.forename: C K
authors.initials: CK
authors.lastname: Meschievitz
authors.forename: G A
authors.initials: GA
authors.lastname: Ballanco
authors.forename: R S
authors.initials: RS
authors.lastname: Daum
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D016667:Bacterial Capsules / Q000276:immunology / Q000652:urine; D001426:Bacterial Proteins / Q000008:administration & dosage; D004168:Diphtheria Toxoid / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D007223:Infant; D011135:Polysaccharides, Bacterial / Q000652:urine; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D010566:Virulence Factors, Bordetella / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D011135:Polysaccharides, Bacterial; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; C061963:HibTITER protein, Haemophilus influenzae