AIDS vaccine: Intranasal immunization using inactivated HIV-1-capturing core-corona type polymeric nanospheres
AIDS vaccine: Intranasal immunization using inactivated HIV-1-capturing core-corona type polymeric nanospheres
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DOI：
10.1016/j.jconrel.2005.09.014
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发表时间：
2005-12-05
影响因子：
10.8
通讯作者：
Akashi, M
中科院分区：
文献类型：
--
作者：
Akagi, T;Ueno, M;Akashi, M
聚合物纳米球已广泛应用于药物、基因和疫苗传递系统等生物医学领域。包埋抗原的纳米球最近被证明具有作为疫苗递送系统和佐剂的巨大潜力。我们曾报道刀豆蛋白A固定的聚苯乙烯纳米球(ConA-NS)能有效捕获HIV-1颗粒，并用灭活的HIV-1捕获纳米球(HIV-NS)诱导小鼠阴道抗HIV-1 IgA抗体应答。此外，经鼻腔免疫的小鼠的阴道洗液能够中和HIV-1。此外，猴/人类免疫缺陷病毒KU-2捕获纳米球(SHIV-NS)免疫的猕猴在阴道和全身感染致病病毒时表现出部分保护作用。HIV-NS被认为特别适合于增强对树突状细胞(DC)的抗原递送。在本研究中，我们用不同大小(360、660、940和1230 nm)的HIV-NS经阴道或鼻腔免疫小鼠，观察了小鼠的黏膜抗体应答。固定化Con A到NS的量取决于颗粒的表面积。此外，不同大小的ConA-NS同样可以捕获灭活的HIV-1。直径360~1230 nm的HIV-NS经阴道或鼻腔免疫可显著诱导阴道抗体反应。而不同大小的HIV-NS经阴道和鼻腔免疫后，阴道抗HIV-1、GP-120、IgA和IgG抗体水平无明显差异。这些结果表明，HIV-NS为诱导粘膜免疫反应和开发粘膜疫苗提供了一种有效的疫苗递送系统。(C)2005 Elsevier B.V.保留所有权利。
Polymeric nanospheres have been widely used in biomedical applications, such as drug, gene and vaccine delivery systems. Nanospheres with entrapped antigens have recently been shown to possess significant potential as vaccine delivery systems and adjuvants. We previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody responses in mice. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1. Moreover, simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) immunized macaques exhibited partial protection when vaginally and systemically challenged with pathogenic viruses. HIV-NS is suggested to be particularly suitable to enhance antigen delivery to dendritic cells (DCs). In this study, we investigated the mucosal antibody response in mice after the intravaginal or intranasal immunization in detail with using different sized (360, 660, 940 and 1230 nm) HIV-NS. The amount of immobilized Con A to NS was dependent on the surface area of the particle. Moreover, Con A-NS with different sizes could equally capture inactivated HIV-1. Intravaginal or intranasal immunization by HIV-NS with diameters ranging 360 to 1230 nm significantly induced vaginal antibody responses. However, significant differences on vaginal anti-HIV-1 gp 120 IgA and IgG antibodies were not found after intravaginal or intranasal immunization with different sized HIV-NS. These results suggest that HIV-NS provides an efficient vaccine delivery system for the induction of a mucosal immune response and the development of a mucosal vaccine. (c) 2005 Elsevier B.V. All rights reserved.