title: Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.
abstract: Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.
authors.affiliation: Division of Clinical Sciences, St. George's University of London, London SW17 0RE, UK. marias@sgul.ac.uk
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Arias
authors.forename: Andrew
authors.initials: A
authors.lastname: Loxley
authors.forename: Christy
authors.initials: C
authors.lastname: Eatmon
authors.forename: Griet
authors.initials: G
authors.lastname: Van Roey
authors.forename: David
authors.initials: D
authors.lastname: Fairhurst
authors.forename: Mark
authors.initials: M
authors.lastname: Mitchnick
authors.forename: Philip
authors.initials: P
authors.lastname: Dash
authors.forename: Tom
authors.initials: T
authors.lastname: Cole
authors.forename: Frank
authors.initials: F
authors.lastname: Wegmann
authors.forename: Quentin
authors.initials: Q
authors.lastname: Sattentau
authors.forename: Robin
authors.initials: R
authors.lastname: Shattock
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology; D014621:Vagina / Q000276:immunology; D014885:Waxes / Q000494:pharmacology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014885:Waxes; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C026344:carnauba wax