Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT.

BACKGROUND AND OBJECTIVE: Premature infants have a higher risk of invasive pneumococcal disease and are more likely to have lower vaccine responses compared with term infants. Increasingly, immunization schedules are including a reduced, 2-dose, pneumococcal conjugate vaccine priming schedule. Our goal was to assess the immunogenicity of 3 commonly used 13-valent pneumococcal conjugate vaccine (PCV13) priming schedules in premature infants and their response to a 12-month booster dose. METHODS: Premature infants (<35 weeks' gestation) were randomized to receive PCV13 at 2 and 4 months (reduced schedule); 2, 3, and 4 months (accelerated schedule); or 2, 4, and 6 months (extended schedule). All infants received a 12-month PCV13 booster. Serotype-specific pneumococcal immunoglobulin G (IgG) for PCV13 serotypes was measured by using enzyme-linked immunosorbent assay 1 month after the primary and booster vaccinations. RESULTS: A total of 210 infants (median birth gestation, 29(+6) weeks; range, 23(+2)-34(+6) weeks) were included. After the primary vaccination, 75% (95% confidence interval [CI], 62-85), 88% (95% CI, 76-95), and 97% (95% CI, 87-99) of participants had protective antibody concentrations for at least one-half the PCV13 serotypes for the reduced, accelerated, and extended schedules, respectively. After the booster vaccination, participants receiving the extended schedule had significantly lower (P < .05) geometric mean concentrations compared with reduced (for 9 of 13 serotypes) and accelerated (for 4 of 13 serotypes) schedules, but nearly all participations, regardless of schedule or serotype, had seroprotective IgG concentrations. CONCLUSIONS: A reduced priming schedule of PCV13 resulted in higher post-booster IgG concentrations but lower post-primary concentrations. The optimum vaccine schedule for preterm infants will therefore depend on when they are most at risk for invasive pneumococcal disease.

Antibody response to diphtheria-tetanus-pertussis immunization in preterm infants who receive dexamethasone for chronic lung disease.

OBJECTIVE: To study the effect of dexamethasone in preterm infants with chronic lung disease (CLD) on antibody response to routine immunization against diphtheria, tetanus, and pertussis (DTP). METHODS: Serum samples were obtained before and after immunization with DTP (Trivax-AD) from an unselected cohort of 93 preterm infants in the United Kingdom. Antibodies to diphtheria and tetanus and to 4 pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin, and fimbrial agglutinogens 2 + 3) were measured by an enzyme-linked immunosorbent assay. Linear regression models were fitted to the natural log of antibody titers to compare the dexamethasone-treated and -untreated infants adjusting for potential risk factors. RESULTS: Sixty-seven (72%) of 93 infants received dexamethasone. Preimmunization geometric mean titers (GMTs) were comparable in both groups for all antibodies. The rise in GMT after immunization was reduced in the dexamethasone-treated group. Final GMT was significantly lower for tetanus, diphtheria, pertussis toxin, and fimbrial agglutinogens 2 + 3 but not for filamentous hemagglutinin or pertactin. Using the minimum protective titer of 0.01 IU/mL, there was no significant reduction in protection for diphtheria and tetanus in the dexamethasone-treated infants. Using the higher reference titer of 0.1 IU/mL, there was a 16% reduction in protection for diphtheria (95% confidence interval: 3%-27%) and a 9% reduction in protection for tetanus (95% confidence interval: -7% to 20%). CONCLUSIONS: The use of dexamethasone for CLD in preterm infants is associated with a reduction in antibody titer to routine immunization against diphtheria and tetanus. Antibody responses to 2 of 4 pertussis antigens are reduced, but the clinical significance of this observation is unclear. Protection against tetanus and diphtheria is not impaired when the lower reference value for protective antibody is used. On the basis of this study of UK preterm infants who were treated with dexamethasone for the management of CLD, we conclude that the current DTP immunization schedule is adequate and do not recommend additional booster protection against tetanus or diphtheria during early infancy. When diphtheria prevalence is increased, however, additional protection should be considered.