title: A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae.
abstract: Infections caused by Streptococcus pneumoniae are a major cause of mortality throughout the world. Protein-based pneumococcal vaccines are envisaged to replace or complement the current polysaccharide-based vaccines. In this context, detoxified pneumolysin (dPly) and pneumococcal histidine triad protein D (PhtD) are two potential candidates for incorporation into pneumococcal vaccines. In this study, the protective efficacy of a PhtD-dPly vaccine was evaluated in a rhesus macaque (Macaca mulatta) model of pneumonia. The animals were immunized twice with 10 μg of PhtD and 10 μg of dPly formulated in the Adjuvant System AS02 or with AS02 alone, before they were challenged with a 19F pneumococcal strain. The survival was significantly higher in the protein-vaccinated group and seemed to be linked to the capacity to greatly reduce bacterial load within the first week post-challenge. Vaccination elicited high concentrations of anti-PhtD and anti-Ply antibodies and a link was found between survival and antibody levels. In conclusion, AS02-adjuvanted PhtD-dPly vaccine protects against S. pneumoniae-induced pneumonia. It is probable that the protection is at least partially mediated by PhtD- and Ply-specific antibodies.
authors.affiliation: GlaxoSmithKline Biologicals, Rixensart, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Denoël
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
authors.forename: Lara
authors.initials: L
authors.lastname: Doyle
authors.forename: Dale
authors.initials: D
authors.lastname: Martin
authors.forename: Georges
authors.initials: G
authors.lastname: Carletti
authors.forename: Jan T
authors.initials: JT
authors.lastname: Poolman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D006867:Hydrolases / Q000008:administration & dosage / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods; D008168:Lung / Q000382:microbiology; D008253:Macaca mulatta; D008297:Male; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000517:prevention & control*; D018419:Primate Diseases / Q000276:immunology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013301:Streptolysins / Q000008:administration & dosage / Q000276:immunology; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; D022223:Vaccines, Subunit; C097552:histidine triad protein; C032290:plY protein, Streptococcus pneumoniae; D006867:Hydrolases