Mechanism for increased immunogenicity of vaccines that form in vivo immune complexes with the natural anti-Gal antibody
Mechanism for increased immunogenicity of vaccines that form in vivo immune complexes with the natural anti-Gal antibody
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DOI：
10.1016/j.vaccine.2009.03.019
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发表时间：
2009-05-18
期刊：
影响因子：
5.5
通讯作者：
Galili, Uri
中科院分区：
文献类型：
--
作者：
Abdel-Motal, Ussama M.;Wigglesworth, Kim;Galili, Uri
抗 Gal 抗体的组成与人体循环 IgG 的 1% 相似，并且与 α-gal 表位特异性相互作用。我们之前报道过，HIV gp120 和流感病毒疫苗上 a-gal 表位的表达可将免疫原性增加约 100 倍。我们假设任何微生物疫苗的免疫原性都可以通过连接的 a-gal 表位显着增加，这是由于体内与抗 Gal 形成免疫复合物以及 APC 通过 Fc/Fc gamma R 相互作用有效内化此类免疫复合物。 APC 内化的抗 Gal 复合疫苗向淋巴结的运输和加工的增加，导致疫苗特异性 CD4(+) 和 CD8(+) T 细胞的有效激活，以及高细胞和体液免疫反应。这种抗 Gal 介导的免疫原性增加的通用机制在以卵清蛋白作为模型疫苗的 α1,3 半乳糖基转移酶敲除小鼠中得到了证实。 (C) 2009 Elsevier Ltd. 保留所有权利。
Anti-Gal constitutes similar to 1% of circulating IgG in humans and interacts specifically with alpha-gal epitopes. We reported previously that expression of a-gal epitopes on HIV gp120 and influenza virus vaccines increases immunogenicity by similar to 100-fold. We hypothesize that immunogenicity of any microbial vaccine can be markedly increased by linked a-gal epitopes due to in vivo formation of immune complexes with anti-Gal and the effective internalization of such immune complexes by APC, via Fc/Fc gamma R interaction. The increased transport to lymph nodes and processing of anti-Gal complexed vaccines internalized by APC, results in effective activation of vaccine specific CD4(+) and CD8(+) T cells, and high cellular and humoral immune response. This universal mechanism for anti-Gal mediated increased immunogenicity is demonstrated in alpha 1,3galactosyltransferase knockout mice with ovalbumin as a model vaccine. (C) 2009 Elsevier Ltd. All rights reserved.