title: Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults.
abstract: BACKGROUND
  Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.
  
  
  OBJECTIVE
  To explore safety and immunogenicity of a recombinant protein vaccine candidate against S. pneumoniae composed of adjuvanted pneumococcal histidine triad protein D (PhtD).
  
  
  METHODS
  This phase I, exploratory, open-label, single-center clinical study enrolled adults (18-50 years). Participants in a pilot safety cohort received a single intramuscular injection of 6 μg. Following safety review, 3 dose cohorts were enrolled (6, 25, and 100 μg); participants received 2 injections administered approximately 30 days apart. Assignment of the second injection and successive dose cohorts were made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events, serious adverse events, and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD antibodies as measured by ELISA.
  
  
  RESULTS
  Sixty-three participants were enrolled and received the pilot safety dose (n=3) or at least 1 dose of PhtD vaccine candidate at 6 μg (n=20), 25 μg (n=20), or 100 μg (n=20). No safety concerns were identified. No vaccine-related serious adverse event was reported. The most common solicited injection site reaction was pain and most common solicited systemic reactions were myalgia and headache; most reactions were mild and transient. Observed geometric mean concentrations (95% CI) were 200.99 ELISA units (148.46, 272.10), 352.07 (193.49, 640.63), and 699.15 (405.49, 1205.48) post-injection 1 in the 6, 25, and 100 μg dose cohorts, respectively, and 378.25 (275.56, 519.21), 837.32 (539.29, 1300.04), and 1568.62 (1082.92, 2272.16) post-injection 2.
  
  
  CONCLUSIONS
  All dose levels were safe and immunogenic. The frequency of solicited reactions was highest at the 100 μg dose. Administration of a second injection significantly increased the levels of anti-PhtD antibodies (ClinicalTrials.gov registry no. NCT01444001).
authors.affiliation: Covance Clinical Research Unit AG, Lettenweg 118, CH-4123 Allschwil, Switzerland. Michael.Seiberling@covance.com
authors.forename: Michael
authors.initials: M
authors.lastname: Seiberling
authors.forename: Monica
authors.initials: M
authors.lastname: Bologa
authors.forename: Roger
authors.initials: R
authors.lastname: Brookes
authors.forename: Martina
authors.initials: M
authors.lastname: Ochs
authors.forename: Kerry
authors.initials: K
authors.lastname: Go
authors.forename: David
authors.initials: D
authors.lastname: Neveu
authors.forename: Thierry
authors.initials: T
authors.lastname: Kamtchoua
authors.forename: Peter
authors.initials: P
authors.lastname: Lashley
authors.forename: Tao
authors.initials: T
authors.lastname: Yuan
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gurunathan
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C097552:histidine triad protein; D006867:Hydrolases