Use of an Sm-p80-Based Therapeutic Vaccine to Kill Established Adult Schistosome Parasites in Chronically Infected Baboons
Use of an Sm-p80-Based Therapeutic Vaccine to Kill Established Adult Schistosome Parasites in Chronically Infected Baboons
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DOI：
10.1093/infdis/jiu031
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发表时间：
2014-06-15
影响因子：
6.4
通讯作者：
Siddiqui, Afzal A.
中科院分区：
文献类型：
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作者：
Karmakar, Souvik;Zhang, Weidong;Siddiqui, Afzal A.
没有疫苗可供人类用于任何寄生虫感染，包括蠕虫病血吸虫病。Sm-p80是曼氏血吸虫钙蛋白酶的大亚基，是血吸虫病疫苗的主要候选抗原。Sm-p80的预防和抗生育功效已在啮齿动物和非人灵长类动物模型中使用多种疫苗方法进行了测试。然而，基于Sm-p80的疫苗的治疗效果尚未确定。在这项研究中，我们通过使用2种不同的策略和3种基于Sm-p80的疫苗制剂在狒狒中评估了Smp-80的治疗效果。与对照制剂相比，疫苗制剂能够使已建立蠕虫减少10%-36%，使组织中的虫卵保留减少10%-57%，并使粪便中的虫卵排泄减少13%-33%。在接种疫苗和对照动物之间观察到B和T细胞免疫相关性的显著差异。这是第一次报道用疫苗杀死已建立的成虫寄生蠕虫。除了Sm-p80的独特预防功效之外，本研究还增加了Sm-p80是具有实质性预防和治疗功效的潜在重要抗原的证据。这些数据强化了Sm-p80应该沿着人类临床试验的道路向前推进。
No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Smp-80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials.