title: Preclinical evaluation of a chemically detoxified pneumolysin as pneumococcal vaccine antigen.
abstract: The use of protein antigens able to protect against the majority of Streptococcus pneumoniae serotypes is envisaged as stand-alone and/or complement to the current capsular polysaccharide-based pneumococcal vaccines. Pneumolysin (Ply) is a key virulence factor that is highly conserved in amino acid sequence across pneumococcal serotypes, and therefore may be considered as a vaccine target. However, native Ply cannot be used in vaccines due to its intrinsic cytolytic activity. In the present work a completely, irreversibly detoxified pneumolysin (dPly) has been generated using an optimized formaldehyde treatment. Detoxi-fication was confirmed by dPly challenge in mice and histological analysis of the injection site in rats. Immunization with dPly elicited Ply-specific functional antibodies that were able to inhibit Ply activity in a hemolysis assay. In addition, immunization with dPly protected mice against lethal intranasal challenge with Ply, and intranasal immunization inhibited nasopharyngeal colonization after intranasal challenge with homologous or heterologous pneumococcal strain. Our findings supported dPly as a valid candidate antigen for further pneumococcal vaccine development.
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Philippe
authors: P
authors: Hermand
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Annick
authors: A
authors: Vandercammen
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Emmanuel
authors: E
authors: Mertens
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Emmanuel
authors: E
authors: Di Paolo
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Vincent
authors: V
authors: Verlant
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Philippe
authors: P
authors: Denoël
authors: a GSK Vaccines , Rixensart , Belgium.
authors: Fabrice
authors: F
authors: Godfroid
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005557:Formaldehyde / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051381:Rats; D013301:Streptolysins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016019:Survival Analysis; D014121:Toxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; D014121:Toxoids; C032290:plY protein, Streptococcus pneumoniae; D005557:Formaldehyde
keywords: Detoxification; Streptococcus pneumoniae; mouse; pneumococcal antigen; pneumolysin; vaccine