Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen

被引:23
作者
Arias, Mauricio A. [1 ]
Loxley, Andrew [2 ]
Eatmon, Christy [2 ]
Van Roey, Griet [1 ]
Fairhurst, David [2 ]
Mitchnick, Mark [2 ]
Dash, Philip [1 ]
Cole, Tom [1 ]
Wegmann, Frank [3 ]
Sattentau, Quentin [3 ]
Shattock, Robin [1 ]
机构
[1] St Georges Univ London, Div Clin Sci, London SW17 0RE, England
[2] Particle Sci Inc, Bethlehem, PA 18017 USA
[3] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
基金
比尔及梅琳达.盖茨基金会; 英国惠康基金;
关键词
HIV; gp140; antigen; Nanoparticles; Mucosal immunity; Vaccines; HUMAN DENDRITIC CELLS; ANIONIC PLG MICROPARTICLES; NASAL IMMUNIZATION; BIODEGRADABLE NANOPARTICLES; NEUTRALIZING ANTIBODIES; VACCINE; VIRUS; INDUCTION; ADJUVANT; DELIVERY;
D O I
10.1016/j.vaccine.2010.11.084
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1258 / 1269
页数:12
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