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

J Nanobiotechnology. 2016 Nov 26;14(1):76. doi: 10.1186/s12951-016-0229-2.

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 × 106 M-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.

Keywords: Scrub typhus; Vaccine; Zinc oxide nanoparticle; ZnO binding peptide.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Biocompatible Materials / chemistry
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Female
  • Metal Nanoparticles / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Orientia tsutsugamushi / immunology
  • Orientia tsutsugamushi / metabolism*
  • Peptides / chemistry
  • Phagocytosis
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Scrub Typhus / prevention & control*
  • Scrub Typhus / veterinary
  • Vaccination
  • Zinc Oxide / chemistry*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Biocompatible Materials
  • Cytokines
  • Peptides
  • Recombinant Proteins
  • Zinc Oxide