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

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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.

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

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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

Ha, N. Y., Shin, H. M., Sharma, P., Cho, H. A., Min, C. K., Kim, H. I., Yen, N. T. H., Kang, J. S., Kim, I. S., Choi, M. S., Kim, Y., & Cho, N. H. (2016). Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen. Journal of Nanobiotechnology, 14(1), [76]. https://doi.org/10.1186/s12951-016-0229-2