Intranasal vaccination using interleukin-12 and cholera toxin subunit B as adjuvants to enhance mucosal and systemic immunity to human immunodeficiency virus type 1 glycoproteins
Intranasal vaccination using interleukin-12 and cholera toxin subunit B as adjuvants to enhance mucosal and systemic immunity to human immunodeficiency virus type 1 glycoproteins
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DOI：
10.1128/jvi.77.10.5589-5597.2003
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发表时间：
2003-05-01
影响因子：
5.4
通讯作者：
Metzger, DW
中科院分区：
文献类型：
--
作者：
Abu, DI;Jones-Trower, A;Metzger, DW
我们研究了通过用 gp120 和 gp140 以及白介素 12 (IL-12) 和霍乱毒素 B 亚基 (CTB) 作为佐剂对小鼠进行鼻内 (i.n) 免疫诱导对人类免疫缺陷病毒 1 型 (HIV-1) 分离株 89.6 的保护性粘膜免疫。结果发现，IL-12 和 CTB 都是引发粘膜抗体反应所必需的，并且 i.n.免疫导致血清中总免疫球蛋白 G1 (IgG1) 和 IgG2a 抗 HIV-1 抗体水平升高；支气管肺泡灌洗液中总抗体、IgG1、IgG2a 和 IgA 表达增加；阴道冲洗液中 IgA 抗体水平增加。在用gp140免疫的组中，血清和分泌物中的抗HIV-1抗体的水平高于用gp120免疫的组。然而，只有 gp120 特异性粘膜抗体表现出针对 HIV-1 89.6 的中和活性。总而言之，结果表明，IL-12 和 CTB 协同作用，增强全身和局部粘膜抗体对 HIV-1 糖蛋白的反应，尽管 gp140 诱导的抗体滴度高于 gp120，但只有 gp120 特异性粘膜抗体会干扰病毒感染性。
We have investigated the induction of protective mucosal immunity to human immunodeficiency virus type 1 (HIV-1) isolate 89.6 by intranasal (i.n.) immunization of mice with gp120 and gp140 together with interleukin-12 (IL-12) and cholera toxin subunit B (CTB) as adjuvants. It was found that both IL-12 and CTB were required to elicit mucosal antibody responses and that i.n. immunization resulted in increased total, immunoglobulin G1 (IgG1), and IgG2a anti-HIV-1 antibody levels in serum; increased total, IgG1, IgG2a, and IgA antibody expression in bronchoalveolar lavage fluids; and increased IgA antibody levels in vaginal washes. Levels of anti-HIV-1 antibodies in both sera and secretions were higher in groups immunized with gp140 than in those immunized with gp120. However, only gp120-specific mucosal antibodies demonstrated neutralizing activity against HIV-1 89.6. Taken together, the results show that IL-12 and CTB act synergistically to enhance both systemic and local mucosal antibody responses to HIV-1 glycoproteins and that even though gp140 induces higher antibody titers than gp120, only gp120-specific mucosal antibodies interfere with virus infectivity.