Center for Tropical Medicine and Infectious Diseases Department of Immunology and Molecular Microbiology.
Department of Natural Sciences, School of Arts and Sciences, Peru State College, Nebraska.
J Infect Dis. 2014 Jun 15;209(12):1929-40. doi: 10.1093/infdis/jiu031. Epub 2014 Jan 16.
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 Sm-p80 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.
目前尚无针对任何寄生虫感染(包括吸虫病血吸虫病)的人类可用疫苗。曼氏血吸虫 calpain 的大亚基 Sm-p80 是血吸虫病疫苗的主要候选抗原。已经使用各种疫苗方法在啮齿动物和非人类灵长类动物模型中测试了 Sm-p80 的预防和抗生育功效。然而,尚未确定基于 Sm-p80 的疫苗的治疗功效。在这项研究中,我们使用 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 Sm-p80 的治疗功效。与对照制剂相比,疫苗制剂可使已建立的成虫减少 10%-36%,使组织中卵的滞留减少 10%-57%,使粪便中卵的排泄减少 13%-33%。在接种疫苗和对照动物之间观察到 B 和 T 细胞免疫相关性存在明显差异。这是首次报道疫苗可杀死已建立的成年血吸虫虫。除了 Sm-p80 的明显预防功效外,本研究还证明 Sm-p80 是一种具有重要预防和治疗功效的潜在重要抗原。这些数据强化了 Sm-p80 应该沿着临床试验的路径向前推进的观点。