Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies
Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies
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DOI：
10.1172/jci11849
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发表时间：
2001-08-01
影响因子：
15.9
通讯作者：
Schiller, JT
中科院分区：
文献类型：
--
作者：
Chackerian, B;Lowy, DR;Schiller, JT
用低剂量的基于病毒样颗粒（VLP）的疫苗对小鼠进行胃肠外接种后，产生了对自身多肽（TNF-α）的高亲和力和持久的自身抗体，所述基于病毒样颗粒的疫苗通过将小鼠TNF-α肽连接到乳头瘤病毒VLP的表面而构建。无论是否联合使用有效的常规佐剂，都可以诱导高滴度自身抗体，但联合使用CFA可以增强高滴度自身抗体。与单独用融合蛋白免疫相比，与VLP的连接使自身抗体滴度增加了1,000倍。对自身（TNF-α）和融合蛋白的外来成分的抗体反应的比较表明，VLP缀合废除了体液免疫系统区分自身和外来的能力。无论抗原的组装状态如何，检测到自身和外源表位的IgM水平相似，表明自身肽与VLP的缀合促进成熟自身反应性B细胞的存活或扩增。在小鼠模型中，接种结合颗粒抑制II型胶原诱导的关节炎的发展。总之，这些结果表明了一种潜在的灵活方法，可以有效地产生针对介导关节炎和其他疾病的特定自身蛋白的自身抗体。
High avidity and long-lasting autoantibodies to a self-polypeptide (TNF-alpha) were generated after parenteral vaccination of mice with low doses of virus-like particle-based (VLP-based) vaccines that were constructed by linking mouse TNF-alpha peptides to the surface of papillomavirus VLPs. High-titer autoantibodies were induced with or without coadministration of potent conventional adjuvants, but were enhanced by coadministration of CFA. Compared with immunization with the fusion protein alone, attachment to VLPs increased autoantibody titers 1,000-fold. A comparison of Ab responses against the self (TNF-alpha) and foreign components of the fusion protein showed that VLP conjugation abrogated the ability of the humoral immune system to distinguish between self and foreign. Similar levels of IgM were detected to self and foreign epitopes regardless of the assembly state of the antigen, suggesting that conjugation of self-peptides to VLPs promotes survival or expansion of mature autoreactive B cells. In a mouse model, vaccination with conjugated particles inhibited development of type II collagen-induced arthritis. Together, these results suggest a potentially flexible method to efficiently generate autoantibodies against specific self-proteins that mediate arthritis and other diseases.