title: Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D-Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media-A Double-Blind Randomized Clinical Trial in Finland.
abstract: After administering the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV) to children aged 2-18 months, we observed a reduction in vaccine-type nasopharyngeal carriage, resulting in a reduction of overall pneumococcal nasopharyngeal carriage, which may be important for indirect vaccine effects. We noted a trend toward reduction of acute otitis media.
  
  
  BACKGROUND
  This trial (ClinicalTrials.gov identifier NCT00839254), nested within a cluster-randomized double-blind invasive pneumococcal disease effectiveness study in Finland (ClinicalTrials.gov identifier NCT00861380), assessed the effectiveness of the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV or PCV10) against bacterial nasopharyngeal carriage and acute otitis media (AOM).
  
  
  METHODS
  Infants (aged 6 weeks to 6 months) received the PHiD-CV or a control vaccine (hepatitis B) (schedule 3+1 or 2+1). Nasopharyngeal swabs were collected at 4 time points post-vaccination from all of the infants and at pre-vaccination from a subset. Parent-reported physician-diagnosed AOM was assessed from first vaccination until last contact (mean follow-up, 18 months). Vaccine effectiveness (VE) was derived as (1 - relative risk)*100, accounting for cluster design in AOM analysis. Significant VE was assessed descriptively (positive lower limit of the non-adjusted 95% confidence interval [CI]).
  
  
  RESULTS
  The vaccinated cohort included 5093 infants for carriage assessment and 4117 infants for AOM assessment. Both schedules decreased vaccine-serotype carriage, with a trend toward a lesser effect from the 2+1 schedule ( VE across timpoints 19%-56% [3+1] and 1%-38% [2+1]). Trends toward reduced pneumococcal carriage (predominantly vaccine serotypes 6B, 14, 19F, and 23F), decreased carriage of vaccine-related serotype 19A, and small increases at later time points (ages 14-15 months) in non-vaccine-serotype carriage were observed. No effects on nontypeable Haemophilus influenzae, Staphylococcus aureus, or Moraxella catarrhalis carriage were observed. There were non-significant trends toward a reduction in the number of infants reporting AOM episodes (VE 3+1: 6.1% [95% CI, -2.7% to 14.1%] and 2+1: 7.4% [-2.8% to 16.6%]) and all AOM episodes (VE 3+1: 2.8% [-9.5% to 13.9%] and 2+1: 10.2% [-4.1% to 22.9%]). PHiD-CV was immunogenic and had an acceptable safety profile.
  
  
  CONCLUSIONS
  We observed reduced vaccine-type pneumococcal carriage, a limited increase in non-vaccine-type carriage, and a trend toward AOM reduction.
authors.affiliation: Vaccine Research Centre , University of Tampere Medical School.
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
authors.affiliation: Vaccine Research Centre , University of Tampere Medical School.
authors.forename: Aino
authors.initials: A
authors.lastname: Forsten
authors.affiliation: Vaccine Research Centre , University of Tampere Medical School.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppä
authors.affiliation: National Institute for Health and Welfare , Oulu.
authors.forename: Tarja
authors.initials: T
authors.lastname: Kaijalainen
authors.affiliation: GSK, Espoo , Finland.
authors.forename: Taneli
authors.initials: T
authors.lastname: Puumalainen
authors.affiliation: GSK, Espoo , Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Soininen
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Magali
authors.initials: M
authors.lastname: Traskine
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lommel
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Sonia
authors.initials: S
authors.lastname: Schoonbroodt
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: Hezareh
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Moreira
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
authors.affiliation: GSK Vaccines, Wavre , Belgium.
authors.forename: Lode
authors.initials: L
authors.lastname: Schuerman
mesh_terms: D004311:Double-Blind Method; D005260:Female; D005387:Finland; D006192:Haemophilus Infections / Q000517:prevention & control*; D006193:Haemophilus influenzae; D006801:Humans; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D010033:Otitis Media / Q000517:prevention & control*; D011008:Pneumococcal Infections; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D013211:Staphylococcus aureus
chemical_list: D022242:Pneumococcal Vaccines
keywords: PHiD-CV; Streptococcus pneumoniae; acute otitis media; nasopharyngeal carriage; pneumococcal conjugate vaccine