An Analysis of 13-Valent Vaccines for Infants

December 17, 2013

Kevin L. Carter

According to the World Health Organization, more than 800,000 children <5 years of age died from pneumococcal disease in 2000, making it the leading vaccine-preventable cause of death worldwide. Since the licensure in 2000 of the first 7-valent pneumococcal polysaccharide conjugate vaccine (PCV) for infants, many countries have added PCV to their existing national immunization programs. As a result, PCV immunization schedules differ between countries with respect to number of doses, age at vaccinations, and intervals between doses. The introduction of PCV has resulted in an overall decline in invasive pneumococcal disease (IPD) in hospitalized children <5 years of age of approximately 60% in Western countries. The optimal vaccine schedule for infants should provide maximal, sustained direct and indirect protection against IPD while using a minimal number of doses.

To assess the optimal priming regimen with respect to antibody induction, the authors investigated the effects of 4 different primary immunization schedules using the 13-valent PCV (PCV13). The study was a single-center, phase 4, randomized, controlled, parallel-group trial conducted in the Netherlands [JAMA. 2013;310(9):930-937]. The aim of the study was to investigate the effects of 4 different primary immunization schedules on the immune response against all serotypes included in PCV13.

Between June 30, 2010, and January 25, 2011, 400 infants were randomly assigned (1:1:1:1) to receive PCV13 either at age 2, 4, and 6 months (subsequently referred to as 2-4-6); at age 3 and 5 months (3-5); at age 2, 3, and 4 months (2-3-4); or at age 2 and 4 months (2-4). All infants received a booster dose of PCV13 at age 11.5 months. Healthy infants born after a gestation period of at least 37 weeks, not yet having received any infant vaccination, and living in the study area in the northwestern part of the Netherlands were eligible for inclusion in the study.

Venous blood samples of 2 mL were collected from all participants at 4 different time points: (1) 1 month after the primary series (postprimary); (2) at 8 months of age; (3) before the booster dose at age 11.5 months; and (4) 1 month after the booster dose. The primary objective was to determine superiority of 1 immunization schedule over another with regard to differences in serotype-specific geometric mean concentrations (GMCs) measured 1 month after the booster dose, at age 12 months.

One month after the booster dose, there were no differences in IgG GMCs between the schedules with the exception of 8 of 78 comparisons. The 2-4-6 schedule was superior to the 2-3-4 schedule for serotypes 18C (10.2 μg/mL [95% confidence interval (CI), 8.2-12.7] vs 6.5 μg/mL [95% CI, 5.4-7.8]) and 23F (10.9 μg/mL [95% CI, 9.0-13.3] vs 7.3 μg/mL [95% CI, 5.8-9.2]) and superior to the 2-4 schedule for serotypes 6B (8.5 μg/mL [95% CI, 7.1-10.2] vs 5.1 μg/mL [95% CI 3.8-6.7]), 18C (6.6 μg/mL [95% CI, 5.7-7.7]), and 23F (7.2 μg/mL [95% CI, 5.9-8.8]). For serotype 1, the 3-5 schedule (11.7 μg/mL [95% CI, 9.6-14.3]) was superior to the other schedules. GMCs for the 13 serotypes ranged between 1.6 μg/mL (95% CI, 1.3-1.9) for serotype 3 in the 2-4-6 schedule and 19.9 μg/mL (95% CI, 16.7-23.7) for serotype 6A in the 2-4 schedule.

The use of 4 different PCV13 immunization schedules in healthy term infants resulted in no statistically significant differences in antibody levels after the booster dose for almost all serotypes.