Effectiveness of the ten-valent pneumococcal Haemophilus influenzae protein D
conjugate vaccine (PHiD-CV10) against invasive pneumococcal disease: a cluster
randomised trial.
Author(s): Palmu AA, Jokinen J, Borys D, Nieminen H, Ruokokoski E, Siira L, Puumalainen T,
Lommel P, Hezareh M, Moreira M, Schuerman L, Kilpi TM.
Affiliation(s): Department of Vaccination and Immune Protection, National Institute for Health
and Welfare, Tampere, Finland. arto.palmu@thl.fi
Publication date & source: 2013, Lancet. , 381(9862):214-22
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: 47,369 children were enrolled from February, 2009, to October, 2010.
30,528 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.
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