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-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity1
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* Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan;
Laboratory for Dendritic Cell Immunology, Research Center for Allergy and Immunology, Institute of Physical and Chemical Research (Japan), Yokohama Institute, Kanagawa, Japan;
Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan;
Department of Molecular Chemistry, Graduate School of Engineering, Osaka University, Osaka, Japan;
¶ Core Research for Evolutional Science and Technology (CREST), the Japan Science and Technology Agency (JST), Tokyo, Japan
Nanoparticles are considered to be efficient tools for inducing potent immune responses by an Ag carrier. In this study, we examined the effect of Ag-carrying biodegradable poly(
-glutamic acid) (-PGA) nanoparticles (NPs) on the induction of immune responses in mice. The NPs were efficiently taken up by dendritic cells (DCs) and subsequently localized in the lysosomal compartments. -PGA NPs strongly induced cytokine production, up-regulation of costimulatory molecules, and the enhancement of T cell stimulatory capacity in DCs. These maturational changes of DCs involved the MyD88-mediated NF-
B signaling pathway. In vivo, -PGA NPs were preferentially internalized by APCs (DCs and macrophages) and induced the production of IL-12p40 and IL-6. The immunization of mice with OVA-carrying NPs induced Ag-specific CTL activity and Ag-specific production of IFN- in splenocytes as well as potent production of Ag-specific IgG1 and IgG2a Abs in serum. Furthermore, immunization with NPs carrying a CD8+ T cell epitope peptide of Listeria monocytogenes significantly protected the infected mice from death. These results suggest that Ag-carrying -PGA NPs are capable of inducing strong cellular and humoral immune responses and might be potentially useful as effective vaccine adjuvants for the therapy of infectious diseases.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Core Research for Evolutional Science and Technology from the Japan Science and Technology Agency.
2 Address correspondence and reprint requests to Dr. Masanori Baba, Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan. E-mail address: m-baba{at}vanilla.ocn.ne.jp
3 Abbreviations used in this paper: DC, dendritic cell; FITC-NP, FITC-labeled -PGA NP; FITC-OVA, FITC-conjugated OVA; FITC-OVA-NP, FITC-OVA-encapsulating NP; iDC, immature DC; LLO, listerolysin; mDC, mature DC; NP, nanoparticle; OVA-NP, OVA-carrying NP; -PGA, poly(-glutamic acid).
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