Division of Clinical Sciences, St. George's University of London, London SW17 0RE, UK.
Vaccine. 2011 Feb 1;29(6):1258-69. doi: 10.1016/j.vaccine.2010.11.084. Epub 2010 Dec 9.
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.
在没有炎症的情况下诱导黏膜部位对 HIV 的体液反应对于疫苗设计很重要。我们开发了带电荷的蜡纳米粒子，它可以有效地吸附蛋白抗原，并在没有炎症的情况下被 DC 内吞。与抗原单独相比，吸附 HIV-gp140 的纳米粒子诱导了更强的体外 T 细胞增殖反应。当抗原与 TLR 配体共同吸附时，这种反应大大增强。在小鼠中的免疫原性研究表明，用 HIV-gp140 抗原吸附的纳米粒子进行皮内接种可诱导高水平的特异性 IgG。重要的是，用吸附 HIV-gp140 的纳米粒子进行鼻内免疫可大大增强血清和阴道 IgG 和 IgA 反应。我们的研究结果表明，携带 HIV-gp140 的蜡纳米粒子可以在没有炎症的情况下诱导强烈的细胞/体液免疫反应，可能作为有效的黏膜佐剂用于 HIV 疫苗候选物。
