title: Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.
abstract: Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.
authors.affiliation: a Medical Research Council Unit ; Banjul , The Gambia.
authors.forename: A
authors.initials: A
authors.lastname: Odutola
authors.affiliation: a Medical Research Council Unit ; Banjul , The Gambia.
authors.forename: M O
authors.initials: MO
authors.lastname: Ota
authors.affiliation: a Medical Research Council Unit ; Banjul , The Gambia.
authors.forename: E O
authors.initials: EO
authors.lastname: Ogundare
authors.affiliation: a Medical Research Council Unit ; Banjul , The Gambia.
authors.forename: M
authors.initials: M
authors.lastname: Antonio
authors.affiliation: a Medical Research Council Unit ; Banjul , The Gambia.
authors.forename: P
authors.initials: P
authors.lastname: Owiafe
authors.affiliation: a Medical Research Council Unit ; Banjul , The Gambia.
authors.forename: A
authors.initials: A
authors.lastname: Worwui
authors.affiliation: b London School of Hygiene & Tropical Medicine ; London , UK.
authors.forename: B
authors.initials: B
authors.lastname: Greenwood
authors.affiliation: c PATH ; Seattle , WA USA.
authors.forename: M
authors.initials: M
authors.lastname: Alderson
authors.affiliation: d GSK Vaccines ; Wavre , Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Traskine
authors.affiliation: d GSK Vaccines ; Wavre , Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Verlant
authors.affiliation: d GSK Vaccines ; Wavre , Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Dobbelaere
authors.affiliation: d GSK Vaccines ; Wavre , Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Borys
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002675:Child, Preschool; D005260:Female; D005714:Gambia; D006801:Humans; D006867:Hydrolases / Q000276:immunology*; D008297:Male; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000009:adverse effects* / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D013301:Streptolysins / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: C586648:10-valent pneumococcal conjugate vaccine; C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; D018074:Vaccines, Conjugate; C097552:histidine triad protein; C032290:plY protein, Streptococcus pneumoniae; D006867:Hydrolases
keywords: Gambian children; immunogenicity; pneumococcal protein; pneumococcal vaccine; safety