title: Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study.
abstract: BACKGROUND
  Acute otitis media is one of the most commonly-diagnosed childhood infections. This study assessed the efficacy of a novel vaccine that contained polysaccharides from 11 different Streptococcus pneumoniae serotypes each conjugated to Haemophilus influenzae-derived protein D in prevention of acute otitis media.
  
  
  METHODS
  4968 infants were randomly assigned to receive either pneumococcal protein D conjugate or hepatitis A vaccine at the ages of 3, 4, 5, and 12-15 months and were followed-up until the end of the second year of life. Middle-ear fluid was obtained for bacteriological culture and serotyping in children who presented with abnormal tympanic membrane or presence of middle-ear effusion, plus two predefined clinical symptoms. The primary endpoint was protective efficacy against the first episode of acute otitis media caused by vaccine pneumococcal serotypes. Analysis was per protocol.
  
  
  RESULTS
  From 2 weeks after the third dose to 24-27 months of age, 333 clinical episodes of acute otitis media were recorded in the protein D conjugate group (n=2455) and 499 in the control group (n=2452), giving a significant (33.6% [95% CI 20.8-44.3]) reduction in the overall incidence of acute otitis media. Vaccine efficacy was shown for episodes of acute otitis media caused by pneumococcal vaccine serotypes (52.6% [35.0-65.5] for the first episode and 57.6% [41.4-69.3] for any episode). Efficacy was also shown against episodes of acute otitis media caused by non-typable H influenzae (35.3% [1.8-57.4]). The vaccine reduced frequency of infection from vaccine-related cross-reactive pneumococcal serotypes by 65.5%, but did not significantly change the number of episodes caused by other non-vaccine serotypes.
  
  
  CONCLUSIONS
  These results confirm that using the H influenzae-derived protein D as a carrier protein for pneumococcal polysaccharides not only allowed protection against pneumococcal otitis, but also against acute otitis media due to non-typable H influenzae. Whether this approach would also allow improved protection against lower respiratory tract infections warrants further investigation.
authors.affiliation: Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. prymula@pmfhk.cz
authors.forename: Roman
authors.initials: R
authors.lastname: Prymula
authors.forename: Pascal
authors.initials: P
authors.lastname: Peeters
authors.forename: Viktor
authors.initials: V
authors.lastname: Chrobok
authors.forename: Pavla
authors.initials: P
authors.lastname: Kriz
authors.forename: Elena
authors.initials: E
authors.lastname: Novakova
authors.forename: Eva
authors.initials: E
authors.lastname: Kaliskova
authors.forename: Igor
authors.initials: I
authors.lastname: Kohl
authors.forename: Patricia
authors.initials: P
authors.lastname: Lommel
authors.forename: Jan
authors.initials: J
authors.lastname: Poolman
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Prieels
authors.forename: Lode
authors.initials: L
authors.lastname: Schuerman
mesh_terms: D000208:Acute Disease; D001426:Bacterial Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D004311:Double-Blind Method; D006193:Haemophilus influenzae / Q000145:classification* / Q000302:isolation & purification / Q000472:pathogenicity; D022362:Hepatitis A Vaccines; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007223:Infant; D008074:Lipoproteins / Q000276:immunology; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D010034:Otitis Media with Effusion / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000276:immunology / Q000627:therapeutic use*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D022362:Hepatitis A Vaccines; D007072:Immunoglobulin D; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C067989:glpQ protein, Haemophilus influenzae