Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen

Na Young Ha, Hyun Mu Shin, Prashant Sharma, Hyun Ah Cho, Chan Ki Min, Hong il Kim, Nguyen Thi Hai Yen, Jae Seung Kang, Ik Sang Kim, Myung Sik Choi, Young-geun Kim, Nam Hyuk Cho

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 (K a =2.26×106M1) 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.

Original languageEnglish
Article number76
JournalJournal of Nanobiotechnology
Volume14
Issue number1
DOIs
Publication statusPublished - 2016 Nov 26

Fingerprint

Orientia tsutsugamushi
Immunization
Zinc Oxide
Antigens
Zinc oxide
Nanoparticles
Immunity
Infection
Peptides
Vaccines
Antibodies
Antibody Formation
Scrub Typhus
Bacterial Antigens
Peptide Library
T-cells

Keywords

  • Scrub typhus
  • Vaccine
  • Zinc oxide nanoparticle
  • ZnO binding peptide

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science

Cite this

Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen. / Ha, Na Young; Shin, Hyun Mu; Sharma, Prashant; Cho, Hyun Ah; Min, Chan Ki; Kim, Hong il; Yen, Nguyen Thi Hai; Kang, Jae Seung; Kim, Ik Sang; Choi, Myung Sik; Kim, Young-geun; Cho, Nam Hyuk.

In: Journal of Nanobiotechnology, Vol. 14, No. 1, 76, 26.11.2016.

Research output: Contribution to journalArticle

Ha, Na Young ; Shin, Hyun Mu ; Sharma, Prashant ; Cho, Hyun Ah ; Min, Chan Ki ; Kim, Hong il ; Yen, Nguyen Thi Hai ; Kang, Jae Seung ; Kim, Ik Sang ; Choi, Myung Sik ; Kim, Young-geun ; Cho, Nam Hyuk. / Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen. In: Journal of Nanobiotechnology. 2016 ; Vol. 14, No. 1.
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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 (K a =2.26×106M1) 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.",
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AU - Ha, Na Young

AU - Shin, Hyun Mu

AU - Sharma, Prashant

AU - Cho, Hyun Ah

AU - Min, Chan Ki

AU - Kim, Hong il

AU - Yen, Nguyen Thi Hai

AU - Kang, Jae Seung

AU - Kim, Ik Sang

AU - Choi, Myung Sik

AU - Kim, Young-geun

AU - Cho, Nam Hyuk

PY - 2016/11/26

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N2 - 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 (K a =2.26×106M1) 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.

AB - 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 (K a =2.26×106M1) 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.

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KW - Zinc oxide nanoparticle

KW - ZnO binding peptide

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