title: Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen.
abstract: The pneumococcal capsule is indispensable for pathogenesis in systemic infections; however, many pneumococcal diseases, including conjunctivitis, otitis media, and some systemic infections in immunocompromised patients, are caused by nonencapsulated Streptococcus pneumoniae (NESp). Null capsule clade 1 (NCC1), found in group 2 NESp, expresses pneumococcal surface protein K (PspK) and is becoming prevalent among pneumococcal organisms owing to the widespread use of pneumococcal conjugate vaccines. Despite its clinical importance, the molecular mechanisms underlying the prevalence of NCC1 have not been fully elucidated. Here, we investigated the role of the R3 domain of PspK in the epithelial cell adherence of NCC1. We found that the R3 domain of PspK mediated NCC1 adherence via its direct interaction with the epithelial surface protein annexin A2. Additionally, neutralization with purified recombinant PspK-R3 or rabbit anti-UD:R3 IgG inhibited binding of NESp to lung epithelial cells in vitro. Immunization with the 'repeat' domain of PspK-R3 or PspK-UD:R3 effectively elicited mucosal and systemic immune responses against PspK-R3 and provided protection against nasopharyngeal, lung, and middle ear colonization of NESp in mice. Additionally, we found that rabbit anti-UD:R3 IgG bound to PspC-R1 of the encapsulated TIGR4 strain and that UD:R3 immunization provided protection against nasopharyngeal and lung colonization of TIGR4 and deaths by TIGR4 and D39 in mice. Further studies using 68 pneumococcal clinical isolates showed that 79% of clinical isolates showed cross-reactivity to rabbit anti-UD:R3 IgG. About 87% of serotypes in the 13-valent pneumococcal conjugate vaccine (PCV) and 68% of non-vaccine serotypes were positive for cross-reactivity with rabbit anti-UD:R3 IgG. Thus, the R3 domain of PspK may be an effective vaccine candidate for both NESp and encapsulated Sp.
authors.affiliation: a Biotechnology Division , Korea Atomic Energy Research Institute , Jeongeup , Republic of Korea.|b Department of Biological Sciences , Chonbuk National University , Jeonju , Republic of Korea.
authors.forename: A-Yeung
authors.initials: AY
authors.lastname: Jang
authors.affiliation: a Biotechnology Division , Korea Atomic Energy Research Institute , Jeongeup , Republic of Korea.
authors.forename: Ho Seong
authors.identifier: 0000-0002-7103-1344
authors.initials: HS
authors.lastname: Seo
authors.affiliation: a Biotechnology Division , Korea Atomic Energy Research Institute , Jeongeup , Republic of Korea.
authors.forename: Shunmei
authors.initials: S
authors.lastname: Lin
authors.affiliation: b Department of Biological Sciences , Chonbuk National University , Jeonju , Republic of Korea.
authors.forename: Gook-Hyun
authors.initials: GH
authors.lastname: Chung
authors.affiliation: c Center for Vaccine Evaluation and Study, Medical Research Institute, School of Medicine , Ewha Womans University , Seoul , Republic of Korea.
authors.forename: Han Wool
authors.initials: HW
authors.lastname: Kim
authors.affiliation: a Biotechnology Division , Korea Atomic Energy Research Institute , Jeongeup , Republic of Korea.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Lim
authors.affiliation: a Biotechnology Division , Korea Atomic Energy Research Institute , Jeongeup , Republic of Korea.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: c Center for Vaccine Evaluation and Study, Medical Research Institute, School of Medicine , Ewha Womans University , Seoul , Republic of Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Park
authors.affiliation: d Department of Microbiology , School of Medicine, Ewha Womans University , Seoul , Republic of Korea.
authors.forename: Jae Hyang
authors.identifier: 0000-0003-0972-9271
authors.initials: JH
authors.lastname: Lim
authors.affiliation: c Center for Vaccine Evaluation and Study, Medical Research Institute, School of Medicine , Ewha Womans University , Seoul , Republic of Korea.|e Department of Pediatrics , School of Medicine, Ewha Womans University , Seoul , Republic of Korea.
authors.forename: Kyung-Hyo
authors.identifier: 0000-0002-0333-6808
authors.initials: KH
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000235:genetics / Q000276:immunology; D000072417:Protein Domains; D011817:Rabbits; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D018074:Vaccines, Conjugate
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C021076:protein K
keywords: Streptococcus pneumoniae; annexin A2; pneumococcal surface protein K; vaccine