Responses to a fourth dose of Haemophilus influenzae type B conjugate vaccine in early life.

OBJECTIVE: To describe the immune response of preterm infants, with a reduced response to primary Haemophilus influenzae type B (Hib) immunisation, to a fourth dose of Hib conjugate vaccine given in early life. DESIGN: Prospective observational study. SETTING: Five Wessex Neonatal Units. PATIENTS: Infants born at < 32 weeks and immunised with three doses of combined acellular pertussis-Hib vaccine, with a Hib IgG geometric mean concentration (GMC) < 1.0 microg/ml after these primary immunisations. INTERVENTIONS: An additional fourth dose of Hib conjugate vaccine given before 1 year of age. Blood taken to assess Hib IgG concentration and avidity after immunisation. MAIN OUTCOME MEASURES: Hib IgG GMC and avidity index. RESULTS: Ninety six infants (mean gestational age at birth 29.1 weeks) received a fourth dose of Hib at a mean age of 7.8 months. Hib IgG GMC after the primary immunisations was 0.17 microg/ml (95% confidence interval (CI) 0.14 to 0.20) rising to 4.68 microg/ml (95% CI 3.36 to 6.57) after the fourth dose (p < 0.0001). The IgG response to the fourth dose correlated positively with the response after the primary immunisations (p < 0.001). Hib IgG geometric mean avidity index (GMAI) after the primary immunisations was 30.87 (95% CI 20.40 to 46.73). This increased to 124.73 (95% CI 109.93 to 141.51) after the fourth dose (p < 0.0001). CONCLUSION: Preterm infants with very low IgG responses to Hib after primary immunisations with a combined acellular pertussis-Hib vaccine mount a good response to a fourth dose of Hib. This study suggests that all infants will benefit from a fourth dose of Hib, regardless of the age at which it is given.

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants.

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.

Antibody to Haemophilus influenzae type b after routine and catch-up vaccination.

Since 1999, the number of cases of Haemophilus influenzae type b (Hib) disease in the UK has risen. We investigated the role of population immunity in this change by testing more than 2600 serum samples from children aged 1-15 years. After the introduction of the routine Hib conjugate vaccination programme for infants, median antibody titres rose significantly in 1-year-olds. Individuals who received their first dose of vaccine at age 1-4 years in the original catch-up campaign initially had much higher concentrations of antibody than those who had been immunised in infancy. A second catch-up campaign in children aged 6 months to 4 years should be highly effective in boosting immunity and reducing disease in the short term.

Immune response of premature infants to meningococcal serogroup C and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b conjugate vaccines.

To determine the immune response of premature infants to meningococcal serogroup C capsular polysaccharide (MCC) and combined diphtheria-tetanus toxoids-acellular pertussis-Haemophilus influenzae type b (DTaP-Hib) conjugate vaccines, 105 infants born at <32 weeks' gestation had Hib IgG geometric mean concentrations (GMCs) and MCC serum bactericidal antibody (SBA) geometric mean titers (GMTs) measured 1 month after the third immunization. Term infants served as control subjects. Premature infants had Hib GMCs of 0.27 microg/mL, with 21% achieving GMCs >1.0 microg/mL, compared with 0.81 microg/mL and 46% in term infants (P<.001 and P=.003, respectively). The MCC SBA GMT was 398, with 99% achieving an SBA > or =8, compared with 380 and 98% in term infants (P=.84 and P=1.0, respectively). Hib IgG was associated with age at third immunization (P<.001). When combined with the DTaP vaccine used in this study, the Hib GMC of premature infants was extremely low. The SBA GMT to MCC was similar to that of term infants.