Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection
Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection
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DOI：
10.1016/j.vaccine.2009.07.013
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发表时间：
2009-09-18
期刊：
影响因子：
5.5
通讯作者：
Rodrigues, Mauricio M.
中科院分区：
文献类型：
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作者：
Haolla, Filipe A.;Claser, Carla;Rodrigues, Mauricio M.
用无鞭毛体表面蛋白2（asp-2）和转唾液酸酶（ts）基因免疫诱导高度易感A/Sn小鼠的保护性免疫，以对抗克氏锥虫Y株的寄生虫感染。基于克氏锥虫的免疫学和生物学菌株变异，我们的目标是使用不同的寄生虫菌株验证我们的疫苗接种结果。由于CD 8（+）T细胞在保护性免疫中的重要性，我们最初确定哪些菌株表达免疫显性H-2K（k）限制性表位TEWETGQI。我们测试了八种菌株，其中四种引起对该表位的免疫应答（Y、G、Colombian和Colombia）。我们选择了哥伦比亚和哥伦比亚菌株进行研究。A/Sn小鼠用不同的方案免疫，使用T. Cruzi基因（ASP-2和TS）同时和随后用血锥鞭毛体攻击。通过特异性抗体和肽特异性T细胞的存在来确认攻击前的免疫应答。基因疫苗接种并没有赋予对致命剂量的哥伦比亚菌株急性感染的保护性免疫力。相反，我们观察到寄生虫血症急剧减少和生存率显着增加，否则致命剂量的哥伦比亚菌株的挑战。在许多存活的晚期慢性感染动物中，我们观察到心脏电导率的变化，与幼稚小鼠相比。总之，我们得出结论，对克氏锥虫抗原的免疫力，类似于病毒和细菌，可能是菌株特异性的，并对疫苗开发产生负面影响。(c)2009爱思唯尔有限公司保留所有权利。
Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain of Trypanosoma cruzi. Based on immunological and biological strain variations in T cruzi parasites, our goal was to validate our vaccination results using different parasite strains. Due to the importance of the CD8(+) T cells in protective immunity, we initially determined which strains expressed the immunodominant H-2K(k)-restricted epitope TEWETGQI. We tested eight strains, four of which elicited immune responses to this epitope (Y, G, Colombian and Colombia). We selected the Colombian and Colombia strains for our studies. A/Sn mice were immunised with different regimens using both T. cruzi genes (asp-2 and ts) simultaneously and subsequently challenged with blood trypomastigotes. Immune responses before the challenge were confirmed by the presence of specific antibodies and peptide-specific T cells. Genetic vaccination did not confer protective immunity against acute infection with a lethal dose of the Colombian strain. In contrast, we observed a drastic reduction in parasitemia and a significant increase in survival, following challenge with an otherwise lethal dose of the Colombia strain. In many surviving animals with late-stage chronic infection, we observed alterations in the heart's electrical conductivity, compared to naive mice. In summary, we concluded that immunity against T cruzi antigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development. (c) 2009 Elsevier Ltd. All rights reserved.