Long-term protective immunity induced against Trypanosoma cruzi infection after vaccination with recombinant adenoviruses encoding amastigote surface protein-2 and trans-sialidase
Long-term protective immunity induced against Trypanosoma cruzi infection after vaccination with recombinant adenoviruses encoding amastigote surface protein-2 and trans-sialidase
复制标题
DOI：
10.1089/hum.2006.17.898
复制
发表时间：
2006-09-01
影响因子：
4.2
通讯作者：
Bruna-Romero, Oscar
中科院分区：
文献类型：
--
作者：
Machado, Alexandre V.;Cardoso, Jarbas E.;Bruna-Romero, Oscar
针对原生动物寄生虫克氏锥虫的保护已经显示依赖于1型免疫应答的诱导。复制缺陷型人5型重组腺病毒具有无与伦比的诱导1型免疫应答的能力。因此，我们构建了两个5型重组腺病毒编码寄生虫抗原转唾液酸酶（rAdTS）和无鞭毛体表面蛋白-2（rAdASP 2）。两种抗原都经过基因工程改造以分泌重组产物，从而诱导最佳抗体和T细胞应答。用rAdASP 2和rAdTS免疫小鼠诱导高水平的针对其重组产物的特异性血清抗体。此外，两种重组病毒都能够引起偏向性辅助T细胞1型（Th 1）细胞免疫应答和大量的CD 8（+）T细胞介导的免疫应答。此外，个体免疫rAdASP 2或rAdTS诱导高水平的保护，对挑战与活的寄生虫。CD 8（+）T细胞至少部分介导了这种保护作用。此外，当在相同的接种物中组合时，rAdTS加rAdASP 2在所有测试的动物中诱导完全保护，即使在最后一次免疫后14周进行攻击时也是如此。这些结果表明，表达T. cruzi是开发针对恰加斯病的疫苗的有趣候选者。
Protection against protozoan parasite Trypanosoma cruzi has been shown to be dependent on the induction of type 1 immune responses. Replication-deficient human type 5 recombinant adenoviruses have an unsurpassed ability to induce type 1 immune responses. Thus, we constructed two type 5 recombinant adenoviruses encoding parasite antigens trans-sialidase (rAdTS) and amastigote surface protein-2 (rAdASP2). Both antigens were genetically engineered to secrete recombinant products in order to induce both optimal antibody and T cell responses. Immunizations of mice with rAdASP2 and rAdTS induced high levels of serum antibodies specific for their recombinant products. In addition, both recombinant viruses were able to elicit a biased helper T cell type 1 (Th1) cellular immune response and a substantial CD8(+) T cell-mediated immune response. Moreover, individual immunization with rAdASP2 or rAdTS induced high levels of protection against a challenge with live parasites. CD8(+) T cells mediated, at least in part, such protection. Furthermore, when combined in the same inoculum, rAdTS plus rAdASP2 induced complete protection in all animals tested, even when challenges were performed 14 weeks after the last immunization. Taking together, these results show that recombinant adenoviruses expressing TS and ASP-2 antigens of T. cruzi are interesting candidates for the development of a vaccine against Chagas' disease.