Poly(gamma-glutamic acid) nanoparticles as an efficient antigen delivery and adjuvant system: potential for an AIDS vaccine.
Antigen delivery systems using polymeric nanoparticles are of special interest as stable protein-based antigen carriers. In the present study, novel biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles were examined for their antigen delivery and immunostimulatory activities in vitro and in vivo. The uptake of ovalbumin by dendritic cells was markedly enhanced by gamma-PGA nanoparticles, and the ovalbumin was gradually released from gamma-PGA nanoparticles into the cells. In addition, gamma-PGA nanoparticles appeared to have great potential as an adjuvant, because they could induce the maturation of dendritic cells. Although not only ovalbumin-encapsulating nanoparticles (OVA-NPs) but also a simple mixture of ovalbumin and nanoparticles induced dendritic cell maturation, the only dendritic cells exposed to OVA-NPs could strongly activate antigen-specific interferon (IFN)-gamma-producing T cells. Subcutaneous immunization of mice with human immunodeficiency virus type 1 (HIV-1) p24-encapsulating nanoparticles activated antigen-specific IFN-gamma-producing T cells in spleen cells and induced p24-specific serum antibodies, as compared to immunization with p24 alone. Like ovalbumin, a mixture of p24 and nanoparticles also induced antigen-specific serum antibodies but did not activate IFN-gamma-producing T cells in spleen cells, suggesting that nanoparticles play a critical role in inducing cellular immune responses. Furthermore, gamma-PGA nanoparticles had a capacity comparable to that of the complete Freund's adjuvant (CFA) in inducing p24-specific serum antibody. However, unlike CFA, they predominantly activated p24-specific IFN-gamma-producing T cells. Thus, gamma-PGA nanoparticles encapsulating various antigens may have great potential as novel and efficient protein-based vaccines against infectious diseases, including HIV-1 infection.
Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Xin
X
Wang
Tomofumi
T
Uto
Takami
T
Akagi
Mitsuru
M
Akashi
Masanori
M
Baba
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000277:Adjuvants, Pharmaceutic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D016503:Drug Delivery Systems; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011099:Polyglutamic Acid / Q000737:chemistry / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000956:Antigens, Viral; D011099:Polyglutamic Acid; D007371:Interferon-gamma; D010047:Ovalbumin