title: Immunization with a combination of three pneumococcal proteins confers additive and broad protection against Streptococcus pneumoniae Infections in Mice.
abstract: Pneumococcal polysaccharide-based vaccines are effective in preventing pneumococcus infection; however, some drawbacks preclude their widespread use in developing and undeveloped countries. Here, we evaluated the protective effects of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (DeltaA146 Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or intranasally challenged with different pneumococcal strains. In intraperitoneal challenge models with pneumococcal strain D39 (serotype 2), the most striking protection was obtained with the combination of the three antigens. Similarly, with the intranasal challenge models, (i) additive clearance of bacteria in lungs was observed for the combination of the three antigens and (ii) a combination vaccine conferred complete protection against intranasal infections of three of the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80% protection for pneumococcal strain 6B. Even so, immunity to this combination could confer protection against pneumococcal infection with a mixture of four serotypes. Our results showed that the combination vaccine was as effective as the currently used vaccines (PCV7 and PPV23). These results indicate that system immunization with the combination of pneumococcal antigens could provide an additive and broad protection against Streptococcus pneumoniae in pneumonia and sepsis infection models.
authors.affiliation: Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, People's Republic of China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Wu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.forename: Miao
authors.initials: M
authors.lastname: Luo
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.forename: Nanlin
authors.initials: N
authors.lastname: Yin
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Wenchun
authors.initials: W
authors.lastname: Xu
authors.forename: Yujuan
authors.initials: Y
authors.lastname: He
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D015169:Colony Count, Microbial; D049071:Endopeptidase Clp; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000276:immunology; D010453:Peptide Synthases / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013301:Streptolysins / Q000276:immunology*; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D050505:Mutant Proteins; D022242:Pneumococcal Vaccines; D013301:Streptolysins; D022223:Vaccines, Subunit; C032290:plY protein, Streptococcus pneumoniae; D012697:Serine Endopeptidases; C501427:ClpP protein, Streptococcus pneumoniae; D049071:Endopeptidase Clp; D010453:Peptide Synthases; C072322:lipoate-protein ligase