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

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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 × 10 6 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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          Most cited references42

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          Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi.

          Orientia tsutsugamushi is the etiological agent of scrub typhus, an acute, mite-borne, febrile illness that occurs in the Asia-Pacific region. Historically, strain characterization used serological analysis and revealed dramatic antigenic diversity. Eyeing a recommendation of potential vaccine candidates for broad protection, we review geographic diversity and serological and DNA prevalences. DNA analysis together with immunological analysis suggest that the prototype Karp strain and closely related strains are the most common throughout the region of endemicity. According to serological analysis, approximately 50% of isolates are seroreactive to Karp antisera, and approximately one-quarter of isolates are seroreactive to antisera against the prototype Gilliam strain. Molecular methods reveal greater diversity. By molecular methods, strains phylogenetically similar to Karp make up approximately 40% of all genotyped isolates, followed by the JG genotype group (Japan strains serotypically similar to the Gilliam strain but genetically non-Gilliam; 18% of all genotyped isolates). Three other genotype groups (Kato-related, Kawasaki-like, and TA763-like) each represent approximately 10% of genotyped isolates. Strains genetically similar to the Gilliam strain make up only 5% of isolates. Strains from these groups should be included in any potential vaccine.
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            Unresolved problems related to scrub typhus: a seriously neglected life-threatening disease.

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              Molecular interaction of proteins and peptides with nanoparticles.

              The interaction of proteins in living cells is one of the key processes in the maintenance of their homeostasis. Introduction of additional agents into the chain of these interactions may influence homeostatic processes. Recent advances in nanotechnologies have led to a wide use of nanoparticles (NPs) in industrial and biomedical applications. NPs are small enough to enter almost all compartments of the body, including cells and organelles, and to complicate the pattern of protein interactions. In some cases, interaction of nanoscale objects with proteins leads to hazardous consequences, such as abnormal conformational changes leading to exposure of cryptic peptide epitopes or the appearance of abnormal functions caused by structural modifications. In addition, the high local protein concentration resulting from protein adsorption on NPs may provoke avidity effects arising from close spatial repetition of the same protein. Finally, the interaction of NPs with proteins is known to induce cooperative effects, such as promotion or inhibition of protein fibrillation or self-assembling of NPs on macromolecules serving as a template. It is obvious that better understanding of the molecular mechanisms of nano-bio interactions is crucial for further advances in all nanotechnological applications. This review summarizes recent progress in understanding the molecular mechanisms of the interactions between proteins or peptides and NPs in order to predict the structural, functional, and/or nanotoxic consequences of these interactions.
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                Author and article information

                Contributors
                nyha6803@snu.ac.kr
                hyunmu.shin@snu.ac.kr
                psharma@snu.ac.kr
                johuna@korea.ac.kr
                kaze78@snu.ac.kr
                oneperson18@snu.ac.kr
                nguyenthihaiyenktyh@gmail.com
                jaeskang@inha.ac.kr
                molecule@plaza.snu.ac.kr
                myung@snu.ac.kr
                +82-2-3290-3281 , ykim97@korea.ac.kr
                +82-2-740-8392 , chonh@snu.ac.kr
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                26 November 2016
                26 November 2016
                2016
                : 14
                : 76
                Affiliations
                [1 ]Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080 Republic of Korea
                [2 ]Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
                [3 ]Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea
                [4 ]Department of Materials Science and Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841 Republic of Korea
                [5 ]Department of Microbiology, Inha University School of Medicine, Incheon, Republic of Korea
                Article
                229
                10.1186/s12951-016-0229-2
                5124320
                27887623
                8223af9d-751c-4ccb-8dab-8bca8a6d7b00
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 September 2016
                : 17 November 2016
                Funding
                Funded by: The National Research Foundation of Korea
                Award ID: 2014M3A7B4052192
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Biotechnology
                zinc oxide nanoparticle,zno binding peptide,scrub typhus,vaccine
                Biotechnology
                zinc oxide nanoparticle, zno binding peptide, scrub typhus, vaccine

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