title: Immunization with Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Provides Protection in a Mouse Model of Colonization.
abstract: Current vaccinations are effective against encapsulated strains of Streptococcus pneumoniae, but they do not protect against nonencapsulated Streptococcus pneumoniae (NESp), which is increasing in colonization and incidence of pneumococcal disease. Vaccination with pneumococcal proteins has been assessed for its ability to protect against pneumococcal disease, but several of these proteins are not expressed by NESp. Pneumococcal surface protein K (PspK), an NESp virulence factor, has not been assessed for immunogenic potential or host modulatory effects. Mammalian cytokine expression was determined in an in vivo mouse model and in an in vitro cell culture system. Systemic and mucosal mouse immunization studies were performed to determine the immunogenic potential of PspK. Murine serum and saliva were collected to quantitate specific antibody isotype responses and the ability of antibody and various proteins to inhibit epithelial cell adhesion. Host cytokine response was not reduced by PspK. NESp was able to colonize the mouse nasopharynx as effectively as encapsulated pneumococci. Systemic and mucosal immunization provided protection from colonization by PspK-positive (PspK(+)) NESp. Anti-PspK antibodies were recovered from immunized mice and significantly reduced the ability of NESp to adhere to human epithelial cells. A protein-based pneumococcal vaccine is needed to provide broad protection against encapsulated and nonencapsulated pneumococci in an era of increasing antibiotic resistance and vaccine escape mutants. We demonstrate that PspK may serve as an NESp target for next-generation pneumococcal vaccines. Immunization with PspK protected against pneumococcal colonization, which is requisite for pneumococcal disease.
authors: Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors: Lance E
authors: LE
authors: Keller
authors: Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors: Xiao
authors: X
authors: Luo
authors: Department of Biological Sciences, Mississippi State University, Mississippi State, Mississippi, USA.
authors: Justin A
authors: JA
authors: Thornton
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.
authors: Keun-Seok
authors: http://orcid.org/0000-0001-9280-9680
authors: KS
authors: Seo
authors: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.
authors: Bo Youn
authors: BY
authors: Moon
authors: Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors: D Ashley
authors: DA
authors: Robinson
authors: Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, Mississippi, USA Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi, USA lmcdaniel@umc.edu.
authors: Larry S
authors: http://orcid.org/0000-0002-1649-7563
authors: LS
authors: McDaniel
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D051379:Mice; D009305:Nasopharynx / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D022242:Pneumococcal Vaccines; D037521:Virulence Factors