Antibody persistence and immunologic memory in children vaccinated with 4 doses of pneumococcal conjugate vaccines: Results from 2 long-term follow-up studies.

To investigate long-term antibody persistence following the administration of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV), we present results of 2 follow-up studies assessing antibody persistence following 2 3+1 schedules up to 4 (NCT00624819 - Study A) and 5 years (NCT00891176 - Study B) post-booster vaccination. In Study A, antibody persistence was measured one, 2 and 4 years post-booster in children previously primed and boosted with PHiD-CV, or primed with the 7-valent pneumococcal conjugate vaccine (7vCRM) and boosted with either PHiD-CV or 7vCRM. In Study B, PHiD-CV was co-administered with meningococcal vaccines, and pneumococcal antibody persistence was measured 2, 3 and 5 years post-booster. An age-matched control group, unvaccinated against Streptococcus pneumoniae, was enrolled in Study A, allowing assessment of immunologic memory by administration of one dose of PHiD-CV to both primed (4 years post-booster) and unprimed 6-year-old children. Four years post-booster (Study A), antibody concentrations and opsonophagocytic activity (OPA) titers remained higher compared to the pre-booster timepoint, with no major differences between the 3 primed groups. Antibody persistence was also observed in Study B, with minimal differences between groups. The additional PHiD-CV dose administered 4 years post-booster in Study A elicited more robust immune responses in primed children than in unprimed children. Long-term serotype-specific antibody persistence and robust immunologic memory responses observed in these 2 studies suggest induction of long-term protection against pneumococcal disease after PHiD-CV vaccination.

Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial.

BACKGROUND: This study evaluated the effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal conjugate vaccine (7vCRM) in young children. METHODS: A randomized controlled trial in the Netherlands, initiated 2 years after 7vCRM introduction, was conducted between 1 April 2008 and 1 December 2010. Infants (N = 780) received either PHiD-CV or 7vCRM (2:1) at 2, 3, 4, and 11-13 months of age. Nasopharyngeal samples taken at 5, 11, 14, 18, and 24 months of age were cultured to detect Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae and S. pneumoniae and confirmed H. influenzae as nontypeable (NTHi). Primary outcome measure was vaccine efficacy (VE) against NTHi colonization. RESULTS: In both groups, NTHi colonization increased with age from 33% in 5-month-olds to 65% in 24-month-olds. Three months postbooster, VE against colonization was 0.5% (95% confidence interval [CI], -21.8% to 18.4%) and VE against acquisition 10.9% (95% CI, -31.3% to 38.9%). At each sampling moment, no differences between groups in either NTHi prevalence or H. influenzae density were detected. Streptococcus pneumoniae (range, 39%-57%), M. catarrhalis (range, 63%--69%), and S. aureus (range, 9%-30%) colonization patterns were similar between groups. CONCLUSIONS: PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or H. influenzae density in healthy Dutch children up to 2 years of age, implying that herd effects for NTHi are not to be expected. Other bacterial colonization patterns were also similar.