A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.
A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis.
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DOI：
10.1371/journal.pone.0013511
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发表时间：
2010-10-20
期刊：
影响因子：
3.7
通讯作者：
Holmdahl R
中科院分区：
文献类型：
--
作者：
Nandakumar KS;Jansson A;Xu B;Rydell N;Ahooghalandari P;Hellman L;Blom AM;Holmdahl R
开发和验证一种重组疫苗，通过持续中和过敏毒素C5 a来减轻关节炎的炎症。我们构建并表达了C5 a与麦芽糖结合蛋白的融合蛋白。在三种不同的关节炎小鼠模型中使用融合蛋白作为疫苗测试特异性C5 a中和的功效：胶原诱导的关节炎（CIA）、慢性复发性CIA和胶原抗体诱导的关节炎（CAIA）。通过ELISA测量抗C5 a抗体和抗II型胶原蛋白的水平。使用用人C5 aR转染的大鼠嗜碱性白血病细胞系进行C5 a中和测定。使用溶血试验测定补体活性，并通过组织学评估关节形态。用MBP-C5 a接种小鼠导致关节炎发病率和严重程度的显著降低，但抗胶原抗体合成没有降低。MBP-C5 a和对照（MBP或PBS）接种的小鼠爪的组织学证实了接种效果。来自接种疫苗的小鼠的血清产生C5 a特异性中和抗体，然而C5活化和C5 b对膜攻击复合物的形成没有显著改变。利用宿主免疫应答产生持续的C5 a中和抗体而不显著损害C5/C5 b活性是用于开发抗体介导的和C5 a依赖性炎性疾病的有效疫苗的有用策略。进一步开发这种治疗性疫苗将是更优化的，并且具有成本效益，以减轻炎症而不影响宿主免疫。
To develop and validate a recombinant vaccine to attenuate inflammation in arthritis by sustained neutralization of the anaphylatoxin C5a. We constructed and expressed fusion protein of C5a and maltose binding protein. Efficacy of specific C5a neutralization was tested using the fusion protein as vaccine in three different arthritis mouse models: collagen induced arthritis (CIA), chronic relapsing CIA and collagen antibody induced arthritis (CAIA). Levels of anti-C5a antibodies and anti-collagen type II were measured by ELISA. C5a neutralization assay was done using a rat basophilic leukemia cell-line transfected with the human C5aR. Complement activity was determined using a hemolytic assay and joint morphology was assessed by histology. Vaccination of mice with MBP-C5a led to significant reduction of arthritis incidence and severity but not anti-collagen antibody synthesis. Histology of the MBP-C5a and control (MBP or PBS) vaccinated mice paws confirmed the vaccination effect. Sera from the vaccinated mice developed C5a-specific neutralizing antibodies, however C5 activation and formation of the membrane attack complex by C5b were not significantly altered. Exploitation of host immune response to generate sustained C5a neutralizing antibodies without significantly compromising C5/C5b activity is a useful strategy for developing an effective vaccine for antibody mediated and C5a dependent inflammatory diseases. Further developing of such a therapeutic vaccine would be more optimal and cost effective to attenuate inflammation without affecting host immunity.
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影响因子：
--
作者：
Fischetti, Fabio;Durigutto, Paolo;Tedesco, Francesco
通讯作者：
Tedesco, Francesco
影响因子：
15.9
作者：
Köhl, J;Baelder, R;Wills-Karp, M
通讯作者：
Wills-Karp, M
影响因子：
--
作者：
HOLMDAHL, R;RUBIN, K;WIGZELL, H
通讯作者：
WIGZELL, H
影响因子：
4.6
作者：
Banda, N. K.;Levitt, B.;Arend, W. P.
通讯作者：
Arend, W. P.
影响因子：
82.9
作者：
Huber-Lang, Markus;Sarma, J. Vidya;Ward, Peter A.
通讯作者：
Ward, Peter A.