Akagi Takami, Kawamura Masaki, Ueno Masamichi, Hiraishi Katsuya, Adachi Masakazu, Serizawa Takeshi, Akashi Mitsuru, Baba Masanori
Japan Immunoresearch Laboratories, Takasaki, Gunma, Japan.
J Med Virol. 2003 Feb;69(2):163-72. doi: 10.1002/jmv.10279.
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.
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。