title: Protection against pneumococcal infection elicited by immunization with multiple pneumococcal heat shock proteins.
abstract: Heat shock proteins (HSPs) play important roles in the pathogenesis of pneumococcal infection, and they are considered as potential protein vaccine antigens. In this study, we investigated the efficacy of immunization with pneumococcal HSPs, including ClpP (hsp100/Clp peptidase subunit), DnaJ (hsp40) and GroEL (hsp60), to protect against pneumococcal carriage, lung colonization and sepsis in mouse models using different serotypes of Streptococcus pneumoniae. In a nasopharyngeal colonization model by serotype 6B or 14 and in a lung colonization model by serotype 19F, immunization with pneumococcal HSPs could elicit effective protection. Likewise, vaccination with ClpP, DnaJ or GroEL allowed significantly longer mouse survival times after lethal intranasal challenge with serotype pneumococcal 2, 3 or 4. Interestingly, combinations of these HSPs could consistently enhance the protection against nasopharynx carriage, lung colonization as well as invasive infection caused by different pneumococcal serotypes. In an in vitro killing assay, anti-sera against ClpP, DnaJ or GroEL could kill S. pneumoniae by polymorphonuclear leukocytes in a complement-dependent way, and combinations of multiple anti-sera against these HSPs could increase the killing ability compared with single anti-sera. Finally, passive immunization studies with anti-sera against pneumococcal HSPs also demonstrated that an additive effect could be achieved by using multiple anti-sera when compared with single anti-sera. Thus, inclusion of multiple pneumococcal HSPs is important for the development of protein-based pneumococcal vaccines.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yali
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Lai
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
authors.forename: Meijuan
authors.initials: M
authors.lastname: Li
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D058491:Bacterial Load / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D049071:Endopeptidase Clp; D050956:HSP40 Heat-Shock Proteins / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology; D007116:Immunization, Passive; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009302:Nasopharyngeal Diseases / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000517:prevention & control; D012697:Serine Endopeptidases / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D022242:Pneumococcal Vaccines; D012697:Serine Endopeptidases; C501427:ClpP protein, Streptococcus pneumoniae; D049071:Endopeptidase Clp
keywords: Heat shock protein; Infection; Streptococcus pneumoniae; Vaccine