Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster randomised trial

Summary Background The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was designed to assess the effectiveness of a pneumococcal vaccine containing ten serotype-specific polysaccharides conjugated to Haemophilus influenzae protein D, tetanus toxoid, and diphtheria toxoid as the carrier proteins (PHiD-CV10) against invasive pneumococcal disease. Methods In this cluster-randomised, double-blind trial, children aged younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants aged younger than 7 months at the first vaccination received either a 3+1 or a 2+1 vaccination schedule, children aged 7–11 months received a 2+1 schedule, and those 12–18 months of age received a two-dose schedule. The primary and secondary objectives were to assess vaccine effectiveness against culture-confirmed invasive pneumococcal disease due to any of the ten vaccine serotypes for the 3+1 and 2+1 schedules, respectively, in children who received at least one PHiD-CV10 dose before 7 months of age. Masked follow-up of pneumococcal disease lasted from the first vaccination (from February, 2009, to October, 2010) to January 31, 2012. Invasive disease data were retrieved from data accumulated in the national infectious diseases register. This trial and the nested acute otitis media trial are registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254, respectively. Findings 47 366 children were enrolled from February, 2009, to October, 2010. 30 527 participants were assessed for the primary objective. 13 culture-confirmed vaccine-type cases of invasive pneumococcal disease were detected: none in the PHiD-CV10 3+1 group, one in the PHiD-CV10 2+1 group, and 12 in the control groups. The estimates for vaccine effectiveness were 100% (95% CI 83–100) for PHiD-CV10 3+1 and 92% (58–100) for PHiD-CV10 2+1 groups. Two cases of any culture-confirmed invasive disease irrespective of serotype were detected in combined PHiD-CV10 infant cohorts compared with 14 in the corresponding control cohorts (vaccine effectiveness 93%, 75–99). In catch-up cohorts, seven cases of invasive disease were reported, all in the control group: two cases in the children enrolled at 7–11 months of age; and five cases in children enrolled at 12–18 months of age (vaccine effectiveness 100%, 79–100). Non-fatal serious adverse events suspected to be vaccine-related were reported via routine post-immunisation safety surveillance in 18 children. Interpretation This nationwide trial showed high PHiD-CV10 effectiveness against invasive pneumococcal disease when given in different schedules. For the first time, effectiveness of a 2+1 schedule in infants was confirmed in a clinical trial. Funding GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare, Finland.