title: Strong T cell type-1 immune responses to HIV-1 Tat (1-72) protein-coated nanoparticles.
abstract: A significant emphasis has been placed on the development of adjuvants and/or delivery systems to improve both antibody production and cell-mediated immune responses. We previously reported on a novel anionic nanoparticle, which led to enhanced humoral and T helper type-1 (Th1) biased immune responses in mice when coated with cationized model antigen. Tat (1-72) is a conserved regulatory HIV-1 protein. It was hypothesized that HIV vaccine strategies employing Tat (1-72) may be a promising approach. Although previous reports have suggested that Tat (1-86) may be immunosuppressive, it was demonstrated in this present study that Tat (1-72) was not immunosuppressive when co-administered to mice with ovalbumin (OVA). Tat (1-72) was coated on novel anionic nanoparticles. BALB/c mice were immunized with Tat (5 microg)-coated nanoparticles (15 microg) by subcutaneous injection on days 0 and 14. Antibody and cytokine release were determined on day 28 and compared to Tat (5 microg) adjuvanted with Alum (15 microg) as a Th2 control, Tat (5 microg) adjuvanted with Lipid A (50 microg) as a Th1 control. Immunization of BALB/c mice with Tat-coated nanoparticles resulted in antibody levels (IgG and IgM) comparable to those elicited from Tat and Alum. However, Tat-coated nanoparticles led to a Th1 biased immune response. The IFN-gamma release from splenocytes with Tat-coated nanoparticles was comparable to that from mice immunized with Tat and Lipid A, and 3.3-fold greater than that from mice immunized with Tat and Alum. These studies warrant further investigation of these nanoparticles to enhance both antibody and cellular-based immune responses.
authors.affiliation: Center for Pharmaceutical Science and Technology, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
authors.forename: Jigna
authors.initials: J
authors.lastname: Patel
authors.forename: Marina
authors.initials: M
authors.lastname: Tuzova
authors.forename: Phillip
authors.initials: P
authors.lastname: Ray
authors.forename: Ryan
authors.initials: R
authors.lastname: Phillips
authors.forename: Jerold G
authors.initials: JG
authors.lastname: Woodward
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Mumper
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D030801:Animals, Genetically Modified; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D036103:Nanotechnology; D010316:Particle Size; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C421254:human immunodeficiency virus type 1 Tat vaccine