title: Induction of potent CD8+ T-cell responses by novel biodegradable nanoparticles carrying human immunodeficiency virus type 1 gp120.
abstract: The mainstream of recent anti-AIDS vaccines is a prime/boost approach with multiple doses of the target DNA of human immunodeficiency virus type 1 (HIV-1) and recombinant viral vectors. In this study, we have attempted to construct an efficient protein-based vaccine using biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs), which are capable of inducing potent cellular immunity. A significant expansion of CD8+ T cells specific to the major histocompatibility complex class I-restricted gp120 epitope was observed in mice intranasally immunized once with gp120-carrying NPs but not with gp120 alone or gp120 together with the B-subunit of cholera toxin. Both the gp120-encapsulating and -immobilizing forms of NPs could induce antigen-specific spleen CD8+ T cells having a functional profile of cytotoxic T lymphocytes. Long-lived memory CD8+ T cells could also be elicited. Although a substantial decay in the effector memory T cells was observed over time in the immunized mice, the central memory T cells remained relatively constant from day 30 to day 238 after immunization. Furthermore, the memory CD8+ T cells rapidly expanded with boosting with the same immunogen. In addition, gamma-PGA NPs were found to be a much stronger inducer of antigen-specific CD8+ T-cell responses than nonbiodegradable polystyrene NPs. Thus, gamma-PGA NPs carrying various HIV-1 antigens may have great potential as a novel priming and/or boosting tool in current vaccination regimens for the induction of cellular immune responses.
authors.affiliation: Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.forename: Takami
authors.initials: T
authors.lastname: Akagi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Masanori
authors.initials: M
authors.lastname: Baba
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000281:Administration, Intranasal; D000818:Animals; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D011099:Polyglutamic Acid / Q000008:administration & dosage* / Q000276:immunology; D011137:Polystyrenes / Q000008:administration & dosage / Q000276:immunology; D013997:Time Factors
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015699:HIV Envelope Protein gp120; D015395:Histocompatibility Antigens Class I; D011137:Polystyrenes; D011099:Polyglutamic Acid