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克氏锥虫 TcTASV-C 蛋白亚家族与 U-Omp19 联合给药可促进小鼠对致死性攻击产生保护反应。

The Trypanosoma cruzi TcTASV-C protein subfamily administrated with U-Omp19 promotes a protective response against a lethal challenge in mice.

机构信息

Instituto de Investigaciones Biotecnológicas (IIBio), Universidad Nacional de San Martín (UNSAM) - CONICET, Av. 25 de Mayo y Francia, Campus UNSAM, San Martín (1650), Provincia de Buenos Aires, Argentina.

出版信息

Vaccine. 2020 Nov 10;38(48):7645-7653. doi: 10.1016/j.vaccine.2020.10.006. Epub 2020 Oct 16.

DOI:10.1016/j.vaccine.2020.10.006
PMID:33071003
Abstract

The development of a Chagaś disease vaccine has yet the need for the identification of novel combinations of antigens and adjuvants. Here, the performance of TcTASV-C proteins that are virulence factors of trypomastigotes and belong to a novel surface protein family specific for T. cruzi, have been evaluated as antigens for a prophylactic vaccine. Several immunization schemes in which TcTASV-C was combined with aluminum hydroxide, saponin and/or U-Omp19 were assayed. Aluminum hydroxide and saponin were assayed together to trigger different pathways of the immune response simultaneously. U-Omp19 is a promising novel adjuvant able to promote a Th1 immune response with IFNg production, thus an interesting molecule to be tested as adjuvant for the control of T. cruzi infection. Therefore, U-Omp19 was added to the aluminum hydroxide-saponin formulation as well as assayed individually with TcTASV-C. The immunization with TcTASV-C and U-Omp19 had the best performance as a prophylactic vaccine. Mice presented the lowest parasitemias and improved survival by 40% after being challenged with a highly virulent T. cruzi strain, which promoted 100% mortality in all other immunized groups. Immunization with TcTASV-C and U-Omp19 triggered cellular responses with IFN-γ and IL-17 production and with lytic antibodies that could explain the protection achieved by this vaccination scheme. To our knowledge, this is the first time that U-Omp19 is tested with a defined T. cruzi antigen in a vaccine formulation.

摘要

尚需鉴定新型抗原和佐剂组合,以开发恰加斯病疫苗。本研究评估了属于锥虫表面蛋白家族的新型虫株表面蛋白 TcTASV-C 作为预防疫苗的抗原,该蛋白是滋养体期的毒力因子。评估了 TcTASV-C 与氢氧化铝、皂苷和/或 U-Omp19 联合的几种免疫方案。同时检测了氢氧化铝和皂苷,以同时触发不同的免疫反应途径。U-Omp19 是一种很有前途的新型佐剂,能够促进产生 IFNg 的 Th1 免疫反应,因此是一种用于控制 T. cruzi 感染的候选佐剂。因此,将 U-Omp19 添加到氢氧化铝-皂苷制剂中,并与 TcTASV-C 分别进行检测。用 TcTASV-C 和 U-Omp19 免疫的效果最好,作为预防疫苗。用高度毒力的 T. cruzi 株攻毒后,感染小鼠的寄生虫血症最低,存活率提高了 40%,而其他所有免疫组的存活率均为 100%。用 TcTASV-C 和 U-Omp19 免疫可引发产生 IFN-γ 和 IL-17 的细胞反应,并产生溶细胞抗体,这可以解释这种疫苗方案所达到的保护效果。据我们所知,这是首次在疫苗配方中用 U-Omp19 测试明确的 T. cruzi 抗原。

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