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用捕获灭活HIV-1的纳米球进行黏膜免疫可在小鼠中诱导显著的HIV-1特异性阴道抗体反应。

Mucosal immunization with inactivated HIV-1-capturing nanospheres induces a significant HIV-1-specific vaginal antibody response in mice.

作者信息

Akagi Takami, Kawamura Masaki, Ueno Masamichi, Hiraishi Katsuya, Adachi Masakazu, Serizawa Takeshi, Akashi Mitsuru, Baba Masanori

机构信息

Japan Immunoresearch Laboratories, Takasaki, Gunma, Japan.

出版信息

J Med Virol. 2003 Feb;69(2):163-72. doi: 10.1002/jmv.10279.

Abstract

Mucosal secretory IgA is considered to have an important role in the prevention of human immunodeficiency virus type 1 (HIV-1) transmission through sexual intercourse. Therefore, substances that induce HIV-1-specific IgA antibody in the genital tract may become promising candidates for prophylactic vaccine against HIV-1 infection. We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and gp120 antigens on their surface and that intravaginal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody in mice. In this study, various strategies for immunization with HIV-NS were undertaken to induce HIV-1-specific IgA response in the mouse genital tract. HIV-NS were administered intravaginally, orally, intranasally or intraperitoneally to mice. Progesterone treatment enhanced the anti-HIV-1 IgA response to intravaginal immunization significantly, but intranasal immunization with HIV-NS was more effective compared with other immunization routes in terms of vaginal IgA response. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1(IIIB). Thus, application of HIV-NS is a practical approach to promote HIV-1-specific IgA response by the vaginal mucosa in the mouse and intranasal appears to be an effective immunization route in this animal model. Intranasal immunization with HIV-NS should be further pursued for its potential as an HIV-1 prophylactic vaccine.

摘要

黏膜分泌型IgA被认为在预防人类免疫缺陷病毒1型(HIV-1)通过性交传播方面发挥着重要作用。因此,能在生殖道诱导产生HIV-1特异性IgA抗体的物质可能成为抗HIV-1感染预防性疫苗的有前景的候选物。我们之前报道过,伴刀豆球蛋白A固定化的聚苯乙烯纳米球(Con A-NS)能够有效捕获其表面的HIV-1颗粒和gp120抗原,并且用灭活的捕获HIV-1的纳米球(HIV-NS)进行阴道免疫可在小鼠体内诱导产生阴道抗HIV-1 IgA抗体。在本研究中,采用了多种HIV-NS免疫策略来在小鼠生殖道诱导产生HIV-1特异性IgA应答。将HIV-NS经阴道、口服、鼻内或腹腔内给予小鼠。孕酮处理显著增强了对阴道免疫的抗HIV-1 IgA应答,但就阴道IgA应答而言,用HIV-NS进行鼻内免疫比其他免疫途径更有效。此外,经鼻内免疫小鼠的阴道灌洗液能够中和HIV-1(IIIB)。因此,应用HIV-NS是促进小鼠阴道黏膜产生HIV-1特异性IgA应答的一种实用方法,并且在该动物模型中鼻内免疫似乎是一种有效的免疫途径。鉴于其作为HIV-1预防性疫苗的潜力,应进一步探索用HIV-NS进行鼻内免疫。

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