title: Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study.
abstract: Conserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants.
  
  
  
  In this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8-10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2-3-4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2-4-9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5-9-12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored.
  
  
  
  1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60-67%) and non-10VT (55-61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI -21.5, 19.5) and 2.1% (-20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (-22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins.
  
  
  
  In this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints.
  
  
  
  PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: aaodutola@mrc.gm.
authors.forename: Aderonke
authors.initials: A
authors.lastname: Odutola
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: otama@who.int.
authors.forename: Martin O C
authors.initials: MOC
authors.lastname: Ota
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: mantonio@mrc.gm.
authors.forename: Martin
authors.initials: M
authors.lastname: Antonio
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: tundeyogundare@yahoo.com.
authors.forename: Ezra O
authors.initials: EO
authors.lastname: Ogundare
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: ysaidu@clintonhealthaccess.org.
authors.forename: Yauba
authors.initials: Y
authors.lastname: Saidu
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: efosternyarko@mrc.gm.
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Foster-Nyarko
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: pkowiafe@uhas.edu.gh.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Owiafe
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: faceesay@mrc.gm.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ceesay
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: aworwui@mrc.gm.
authors.forename: Archibald
authors.initials: A
authors.lastname: Worwui
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: oidoko@mrc.gm.
authors.forename: Olubukola T
authors.initials: OT
authors.lastname: Idoko
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: oowolabi@mrc.gm.
authors.forename: Olumuyiwa
authors.initials: O
authors.lastname: Owolabi
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: ambojang@mrc.gm.
authors.forename: Abdoulie
authors.initials: A
authors.lastname: Bojang
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: shjarju@mrc.gm.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Jarju
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: idrammeh@mrc.gm.
authors.forename: Isatou
authors.initials: I
authors.lastname: Drammeh
authors.affiliation: Medical Research Council Unit, Vaccines & Immunity Theme, Banjul, Gambia. Electronic address: bkampmann@mrc.gm.
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: Brian.Greenwood@lshtm.ac.uk.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
authors.affiliation: PATH, Seattle, WA, USA. Electronic address: malderson@path.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Alderson
authors.affiliation: GSK, Wavre, Belgium. Electronic address: magali.x.traskine@gsk.com.
authors.forename: Magali
authors.initials: M
authors.lastname: Traskine
authors.affiliation: GSK, Wavre, Belgium. Electronic address: nathalie.i.devos@gsk.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Devos
authors.affiliation: GSK, Wavre, Belgium. Electronic address: sonia.j.schoonbroodt@gsk.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Schoonbroodt
authors.affiliation: GSK, Wavre, Belgium. Electronic address: kristien.m.swinnen@gsk.com.
authors.forename: Kristien
authors.initials: K
authors.lastname: Swinnen
authors.affiliation: GSK, Wavre, Belgium. Electronic address: vincent.verlant@gsk.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Verlant
authors.affiliation: GSK, Wavre, Belgium. Electronic address: dobbelaerekurt@gmail.com.
authors.forename: Kurt
authors.initials: K
authors.lastname: Dobbelaere
authors.affiliation: GSK, Wavre, Belgium. Electronic address: dorota.d.borys@gsk.com.
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
mesh_terms: D058491:Bacterial Load; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D002353:Carrier State / Q000517:prevention & control*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005714:Gambia; D006801:Humans; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D016037:Single-Blind Method; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification; D016896:Treatment Outcome
chemical_list: D001426:Bacterial Proteins; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines
keywords: Infant; Nasopharyngeal carriage; Pneumococcal histidine triad protein D; Pneumolysin; Streptococcus pneumoniae; Vaccine efficacy