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 aff...

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Main Authors: 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 Keun Kim, Nam-Hyuk Cho
Format: Article
Language:English
Published: BMC 2016-11-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12951-016-0229-2
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author 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 Keun Kim
Nam-Hyuk Cho
author_facet 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 Keun Kim
Nam-Hyuk Cho
author_sort Na-Young Ha
collection DOAJ
description 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.
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spelling doaj.art-d947d68f74304041bf8c4a4d1ac2ff162022-12-22T02:56:33ZengBMCJournal of Nanobiotechnology1477-31552016-11-0114111210.1186/s12951-016-0229-2Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigenNa-Young Ha0Hyun Mu Shin1Prashant Sharma2Hyun Ah Cho3Chan-Ki Min4Hong-il Kim5Nguyen Thi Hai Yen6Jae-Seung Kang7Ik-Sang Kim8Myung-Sik Choi9Young Keun Kim10Nam-Hyuk Cho11Department of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Materials Science and Engineering, Korea UniversityDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Microbiology, Inha University School of MedicineDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Microbiology and Immunology, Seoul National University College of MedicineDepartment of Materials Science and Engineering, Korea UniversityDepartment of Microbiology and Immunology, Seoul National University College of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12951-016-0229-2Zinc oxide nanoparticleZnO binding peptideScrub typhusVaccine
spellingShingle 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 Keun Kim
Nam-Hyuk Cho
Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen
Journal of Nanobiotechnology
Zinc oxide nanoparticle
ZnO binding peptide
Scrub typhus
Vaccine
title Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen
title_full Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen
title_fullStr Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen
title_full_unstemmed Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen
title_short Generation of protective immunity against Orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with ScaA antigen
title_sort generation of protective immunity against orientia tsutsugamushi infection by immunization with a zinc oxide nanoparticle combined with scaa antigen
topic Zinc oxide nanoparticle
ZnO binding peptide
Scrub typhus
Vaccine
url http://link.springer.com/article/10.1186/s12951-016-0229-2
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