title: Safety, reactogenicity and immunogenicity of a novel pneumococcal protein-based vaccine in adults: a phase I/II randomized clinical study.
abstract: BACKGROUND
  New vaccines containing highly conserved Streptococcus pneumoniae proteins such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) are being developed to provide broader protection against pneumococcal disease. This study evaluated the safety, reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults.
  
  
  METHODS
  In a phase I double-blind study (www.clinicaltrials.gov: NCT00707798), healthy adults (18-40 years) were randomized (1:2:2:2:2:2:2) to receive two doses of one of six investigational vaccine formulations 2 months apart, or a single dose of the control 23-valent pneumococcal polysaccharide vaccine (23PPV; Pneumovax23™, Sanofi Pasteur MSD) followed by placebo. The investigational formulations contained dPly alone (10 or 30 μg), or both dPly and PhtD (10 or 30 μg each) alone or combined with the polysaccharide conjugates of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Vaccines). Two groups primed with a formulation containing dPly and PhtD (10 or 30 μg each) continued to the follow-up phase II study (NCT00896064), in which they received a booster dose at 5-9 months after primary vaccination.
  
  
  RESULTS
  Of 156 enrolled and vaccinated adults, 146 completed the primary immunization and 43 adults received a booster dose. During primary and booster vaccination, for any formulation, ≤ 8.9% of doses were followed by grade 3 solicited local or general adverse events. No fever >39.5°C (oral temperature) was reported. Unsolicited adverse events considered causally related to vaccination were reported following ≤ 33.3% of investigational vaccine doses. No serious adverse events were reported for adults receiving investigational vaccine formulations. Formulations containing dPly with or without PhtD were immunogenic for these antigens; polysaccharide conjugate-containing formulations were also immunogenic for those 10 polysaccharides.
  
  
  CONCLUSIONS
  Investigational vaccine formulations containing dPly and PhtD were well tolerated and immunogenic when administered to healthy adults as standalone protein vaccine or combined with PHiD-CV conjugates.
authors.affiliation: Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium. Electronic address: Geert.LerouxRoels@UGent.be.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium. Electronic address: Cathy.Maes@UZGent.be.
authors.forename: Cathy
authors.initials: C
authors.lastname: Maes
authors.affiliation: Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium. Electronic address: Fien.DeBoever@UZgent.be.
authors.forename: Fien
authors.initials: F
authors.lastname: De Boever
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium. Electronic address: Magali.x.traskine@gsk.com.
authors.forename: Magali
authors.initials: M
authors.lastname: Traskine
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium. Electronic address: jrueggeberg@doctors.org.uk.
authors.forename: Jens U
authors.initials: JU
authors.lastname: Rüggeberg
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium. Electronic address: dorota.d.borys@gsk.com.
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D006867:Hydrolases / Q000276:immunology; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D013301:Streptolysins / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D010919:Placebos; D022242:Pneumococcal Vaccines; D013301:Streptolysins; C097552:histidine triad protein; C032290:plY protein, Streptococcus pneumoniae; D006867:Hydrolases
keywords: PhtD; Pneumococcal protein-containing vaccine; Pneumolysin; Streptococcus pneumoniae; dPly