title: Vaccination with a Streptococcus pneumoniae trivalent recombinant PcpA, PhtD and PlyD1 protein vaccine candidate protects against lethal pneumonia in an infant murine model.
abstract: Streptococcus pneumoniae infections continue to cause significant worldwide morbidity and mortality despite the availability of efficacious serotype-dependent vaccines. The need to incorporate emergent strains expressing additional serotypes into pneumococcal polysaccharide conjugate vaccines has led to an identified need for a pneumococcal protein-based vaccine effective against a broad scope of serotypes. A vaccine consisting of several conserved proteins with different functions during pathogenesis would be preferred. Here, we investigated the efficacy of a trivalent recombinant protein vaccine containing pneumococcal choline-binding protein A (PcpA), pneumococcal histidine triad D (PhtD), and genetically detoxified pneumolysin (PlyD1) in an infant mouse model. We found the trivalent vaccine conferred protection from lethal pneumonia challenges using serotypes 6A and 3. The observed protection with trivalent PcpA, PhtD, and PlyD1 vaccine in infant mice supports the ongoing study of this candidate vaccine in human infant clinical trials.
authors.affiliation: Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, United States.
authors.forename: David
authors.initials: D
authors.lastname: Verhoeven
authors.affiliation: Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, United States.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Rochester General Hospital Research Institute, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621, United States. Electronic address: Michael.Pichichero@rochestergeneral.org.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D005260:Female; D006867:Hydrolases / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D018805:Sepsis / Q000517:prevention & control; D013301:Streptolysins / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; C113653:PcpA protein, Streptococcus; D022242:Pneumococcal Vaccines; D011994:Recombinant Proteins; D013301:Streptolysins; D018074:Vaccines, Conjugate; C097552:histidine triad protein; C032290:plY protein, Streptococcus pneumoniae; D006867:Hydrolases
keywords: Infant vaccination; Pneumococcal choline binding protein A; Pneumococcal histidine triad D protein; Pneumolysin; Streptococcus pneumoniae