Randomised trial of the effect of co-administration with acellular pertussis DTP vaccine on immunogenicity of Haemophilus influenzae type b conjugate vaccine

Lancet. 1996 Dec;348(9043):1688-92. doi: 10.1016/S0140-6736(96)04356-5.

Abstract

Background: Inclusion of new vaccines in vaccination programmes for children would be easier if they could be combined with existing vaccines. Vaccines containing acellular pertussis in the diphtheria/tetanus/pertussis (DTP-a) combination are expected to replace the conventional whole-cell vaccines (DTP-w). We tested the immunogenicity and safety of a combination of DTP-a with the Haemophilus influenzae type b (Hib) conjugate of Hib capsular polysaccharide and tetanus toxid (PRP-T), and inactivated poliovirus vaccine (i.p.v.).

Methods: 120 infants were enrolled and randomised to four groups to receive DTP-a at ages 2, 4, and 6 months. At 4 and 6 months they also received Hib conjugate and i.p.v., either as separate injections or mixed with DTP-a. All injections were given intramuscularly in the anterolateral area of the thigh. Any reactions after each vaccination were noted by the parents. EIA was used to measure titres of diphtheria, tetanus, and pertussis antibodies, RIA for Hib anticapsular antibodies, and microneutralisation assay for poliovirus antibodies from serum samples collected at the ages of 2, 4, 6, and 7 months.

Findings: There were 30 infants in each group. Only mild adverse events were reported. There was a tendency towards slightly lower concentrations of filamentous haemagglutinin, tetanus, and poliovirus 1 antibodies when the vaccines were mixed. However, there was a more pronounced difference (p = 4 x 10(-6)) in Hib antibodies between groups receiving Hib capsular polysaccharide mixed with DTP-a (geometric mean concentrations 0.37 microgram/mL and 0.56 microgram/mL) compared with groups receiving the vaccines separately (3.10 micrograms/mL and 3.94 micrograms/mL).

Interpretation: Administration of premixed DTP-a, Hib conjugate, and i.p.v. affect the immune response significantly. The mechanism of this interference is not clear. The immunogenicity of all antigens must be tested before new combinations can be accepted for vaccination programmes for infants.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • Bacterial Capsules
  • Diphtheria / immunology
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology*
  • Haemophilus Infections / immunology
  • Haemophilus Vaccines / administration & dosage
  • Haemophilus Vaccines / immunology*
  • Humans
  • Infant
  • Poliovirus / immunology
  • Poliovirus Vaccine, Inactivated / immunology
  • Polysaccharides, Bacterial / administration & dosage
  • Polysaccharides, Bacterial / immunology*
  • Tetanus / immunology
  • Tetanus Toxoid / immunology
  • Vaccination / methods*
  • Vaccines, Conjugate / administration & dosage
  • Vaccines, Conjugate / immunology*

Substances

  • Antibodies, Bacterial
  • Antibodies, Viral
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate
  • Haemophilus influenzae type b polysaccharide vaccine
  • Poliovirus Vaccine, Inactivated
  • Polysaccharides, Bacterial
  • Tetanus Toxoid
  • Vaccines, Conjugate