title: Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen.
abstract: BACKGROUND
  Zinc oxide nanoparticle (ZNP) has been applied in various biomedical fields. Here, we investigated the usage of ZNP as an antigen carrier for vaccine development by combining a high affinity peptide to ZNP.
  
  
  RESULTS
  A novel zinc oxide-binding peptide (ZBP), FPYPGGDA, with high affinity to ZNP (Ka= 2.26 × 106M-1) was isolated from a random peptide library and fused with a bacterial antigen, ScaA of Orientia tsutsugamushi, the causative agent of scrub typhus. The ZNP/ZBP-ScaA complex was efficiently phagocytosed by a dendritic cell line, DC2.4, in vitro and significantly enhanced anti-ScaA antibody responses in vivo compared to control groups. In addition, immunization with the ZNP/ZBP-ScaA complex promoted the generation of IFN-γ-secreting T cells in an antigen-dependent manner. Finally, we observed that ZNP/ZBP-ScaA immunization provided protective immunity against lethal challenge of O. tsutsugamushi, indicating that ZNP can be used as a potent adjuvant when complexed with ZBP-conjugated antigen.
  
  
  CONCLUSIONS
  ZNPs possess good adjuvant potential as a vaccine carrier when combined with an antigen having a high affinity to ZNP. When complexed with ZBP-ScaA antigen, ZNPs could induce strong antibody responses as well as protective immunity against lethal challenges of O. tsutsugamushi. Therefore, application of ZNPs combined with a specific soluble antigen could be a promising strategy as a novel vaccine carrier system.
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Ha
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.|Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea.
authors.forename: Hyun Mu
authors.initials: HM
authors.lastname: Shin
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Prashant
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Department of Materials Science and Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chan-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hong-Il
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Nguyen Thi Hai
authors.initials: NT
authors.lastname: Yen
authors.affiliation: Department of Microbiology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea.
authors.forename: Ik-Sang
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.|Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea.
authors.forename: Myung-Sik
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Department of Materials Science and Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea. ykim97@korea.ac.kr.
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. chonh@snu.ac.kr.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. chonh@snu.ac.kr.|Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea. chonh@snu.ac.kr.
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001672:Biocompatible Materials / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D012285:Orientia tsutsugamushi / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D012612:Scrub Typhus / Q000517:prevention & control* / Q000662:veterinary; D014611:Vaccination; D015034:Zinc Oxide / Q000737:chemistry*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001672:Biocompatible Materials; D016207:Cytokines; D010455:Peptides; D011994:Recombinant Proteins; D015034:Zinc Oxide
keywords: Scrub typhus; Vaccine; Zinc oxide nanoparticle; ZnO binding peptide