Cubillos Carolina, de la Torre Beatriz G, Jakab Annamaria, Clementi Giorgia, Borrás Eva, Bárcena Juan, Andreu David, Sobrino Francisco, Blanco Esther
Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain.
J Virol. 2008 Jul;82(14):7223-30. doi: 10.1128/JVI.00401-08. Epub 2008 Apr 30.
The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptide-immunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.
本文描述了一种树枝状肽成功用于保护猪免受口蹄疫病毒（FMDV）攻击的情况，口蹄疫病毒可引发全球最具毁灭性的动物疾病。用含有一个口蹄疫病毒T细胞表位拷贝并分支为四个B细胞表位拷贝的肽对动物进行肌肉注射免疫。四只免疫猪在受到口蹄疫病毒攻击后未出现明显临床症状，既无全身性也无黏膜性口蹄疫病毒复制，也未观察到其向接触对照猪的传播。树枝状结构特异性诱导了高滴度的口蹄疫病毒中和抗体并激活了口蹄疫病毒特异性T细胞。有趣的是，尽管肽是通过肠胃外给药，但仍观察到了强效的抗口蹄疫病毒免疫球蛋白A反应（局部和全身）。另一方面，肽免疫动物未显示出口蹄疫病毒感染特异性抗体，这使该肽有资格成为一种潜在的标记疫苗。总体而言，所使用的树枝状肽引发的免疫反应与对照口蹄疫病毒感染猪的免疫反应相当，这与对口蹄疫病毒攻击的可靠保护相关。这种类型的树枝状设计可能为肽亚单位疫苗的开发带来巨大希望。
