Modulation of innate and adaptive immunity by biodegradable nanoparticles.
Vaccine strategy needs efficient adjuvants to induce potent antigen-specific immune responses by targeting antigens to antigen presenting cells followed by their functional maturation. In this study, biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) were examined for their immunological activities in mice. Like lipopolysaccharide, gamma-PGA NPs strongly activated spleen dendritic cells (DCs) and induced their cytokine production and costimulatory molecule expression through the nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways. The immunization of mice with ovalbumin-carrying gamma-PGA NPs could induce the antigen-specific and long-lived effector and central memory CD8(+) T cells as well as antibody responses. Thus, gamma-PGA NPs have great potential as an efficient antigen carrier and strong adjuvant to DCs.
Uto
Tomofumi
T
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Akagi
Takami
T
Hamasaki
Takayuki
T
Akashi
Mitsuru
M
Baba
Masanori
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D007110:Immunity, Active / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects*; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D053758:Nanoparticles; D010047:Ovalbumin / Q000276:immunology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D010047:Ovalbumin; D020928:Mitogen-Activated Protein Kinases