ArticlesEffectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial
Introduction
Widespread use of the first seven-valent pneumococcal non-toxic diphtheria-toxin analogue-conjugate vaccine (PCV7; Prevenar/Prevnar, Pfizer, Philadelphia, PA, USA) has resulted in significant reduction of invasive pneumococcal disease among vaccinated children on several continents.1, 2, 3, 4, 5, 6 Invasive pneumococcal disease has also decreased among unvaccinated populations (herd protection). However, an increase in invasive disease caused by pneumococcal serotypes other than those contained in the vaccine (replacement) has been detected both in vaccinated and unvaccinated populations.4, 5, 6, 7
Another pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins was developed (PHiD-CV10).8, 9, 10 The vaccine was licensed in the European Union in March, 2009, (Synflorix, GlaxoSmithKline Vaccines, Rixensart, Belgium) on the basis of PHiD-CV10 immunological data according to criteria recommended by WHO11 for licensure for protection against invasive pneumococcal disease, PHiD-CV10 safety data, and efficacy results of the 11-valent precursor formulation against acute otitis media.12
The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the clinical vaccine effectiveness of PHiD-CV10 against invasive pneumococcal disease. To enable unbiased assessment of the total effectiveness in vaccinated children and subsequently the indirect effectiveness in unvaccinated populations we used a cluster randomised clinical field-trial design. Here, we report the effectiveness of PHiD-CV10 against invasive pneumococcal disease in vaccinated children.
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Trial design and participants
The FinIP vaccine trial is a controlled, cluster-randomised, double-blind, field trial done in Finnish health-care centres. The study was designed to assess the effectiveness of the PHiD-CV10 against invasive pneumococcal disease in infants. A parallel acute otitis media trial done by the Tampere University Vaccine Research Centre (TAUVRC) had the same cluster-randomised design and its participants were also assessed in this study.13
In August, 2008, public municipal health-care centres in
Results
From February 18, 2009, to October 5, 2010, a total of 47 366 children were enrolled (figure). Of the roughly 125 000 children invited to participate, 38% were finally enrolled. Enrolment proportion ranged from 21–61% in the 72 well-baby-clinic clusters and from 8–16% in the six TAUVRC-only clusters.
All 45 974 participants who received at least one dose of correct vaccine were included in intention-to-treat analyses. 1392 children were excluded from effectiveness analysis: 1381 children did not
Discussion
The FinIP trial showed effectiveness of the PHiD-CV10 vaccine against invasive pneumococcal disease for all vaccination schedules assessed. The effectiveness of the infant 2+1 schedule used in many national programmes was shown for the first time in a clinical-trial setting (panel). Effectiveness was also shown against the two most common serotypes 6B and 14. We were not able to show serotype-specific effectiveness for any of the other serotypes (including the additional serotypes 1, 5, and 7F
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