Targeting of antigen to dendritic cells with poly(gamma-glutamic acid) nanoparticles induces antigen-specific humoral and cellular immunity.
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(gamma-glutamic acid) (gamma-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. gamma-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-kappaB signaling pathway. In vivo, gamma-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-gamma 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 gamma-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.
Uto
Tomofumi
T
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
Wang
Xin
X
Sato
Katsuaki
K
Haraguchi
Misako
M
Akagi
Takami
T
Akashi
Mitsuru
M
Baba
Masanori
M
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry; D011099:Polyglutamic Acid / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011099:Polyglutamic Acid