Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster

Lancet. 1997 Apr 26;349(9060):1197-202. doi: 10.1016/s0140-6736(96)06392-1.

Abstract

Background: Diseases of early childhood associated with Haemophilus influenzae type b (Hib) can now be prevented by vaccination. The rapid implementation of routine infant vaccination with Hib polysaccharide-tetanus protein conjugate (PRP-T) vaccine has allowed us to assess whether an accelerated 2, 3, and 4 month schedule can protect in the longer term without a booster dose and whether carrier priming influences protective efficacy. The degree of protection afforded by a catch-up programme with Hib oligosaccharide conjugate (HbOC) for older children was also assessed.

Methods: Paediatricians and microbiologists in the UK were asked to report all cases of invasive H influenzae infection in children who had received at least one dose of Hib-conjugate vaccine. Serum samples from convalescent children were obtained and the isolate was verified. Efficacy was estimated by comparing observed rates of Hib disease in those who had been vaccinated with rates predicted by age adjustment of disease rates from the prevaccine era.

Findings: Of 164 reports of invasive infection between Oct 1, 1992, and Oct 1, 1995, 43 were considered true vaccine failures. The estimated overall efficacy for three doses of PRP-T was 98.1% (95% CI 97.3-98.7%). Efficacy in infants aged 5-11 months was 99.1%, 12-23 months 97.3%, and 24-35 months 94.7%. In infants aged 3-11 months, who received their first dose of PRP-T after tetanus toxoid vaccination, disease was unlikely from 1 week after one dose of PRP-T vaccine (88.6% protection in the second to fourth weeks [66.8-97.7%]). The disease rate in vaccinated infants aged 2 months has declined year on year. In children aged 13 months to 2 years given HbOC, as a catch-up vaccine, the estimated efficacy was 94.0% (84.7-98.4%).

Interpretation: A high degree of efficacy has been observed with PRP-T vaccine given as a three-dose schedule in infancy and with HbOC as a single dose in older children. Efficacy of PRP-T appears to be enhanced by carrier priming. Although with increasing age there was a small decline in efficacy of PRP-T, Hib disease is now close to being eliminated in the UK, and we suggest that a booster is not necessary in the second year of life.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antibodies, Bacterial / blood
  • Child, Preschool
  • Forecasting
  • Haemophilus Infections / immunology
  • Haemophilus Infections / prevention & control
  • Haemophilus Vaccines / administration & dosage*
  • Haemophilus influenzae* / classification
  • Haemophilus influenzae* / immunology
  • Humans
  • Immunization Schedule
  • Immunization*
  • Immunization, Secondary*
  • Incidence
  • Infant
  • Prospective Studies
  • Tetanus Toxoid / administration & dosage*
  • Treatment Failure
  • United Kingdom
  • Vaccination
  • Vaccines, Conjugate / administration & dosage*

Substances

  • Antibodies, Bacterial
  • Haemophilus Vaccines
  • Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate
  • Tetanus Toxoid
  • Vaccines, Conjugate