T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum
T-helper-2 cytokine responses to Sj97 predict resistance to reinfection with Schistosoma japonicum
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DOI：
10.1128/iai.74.1.370-381.2006
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Kurtis, JD
中科院分区：
文献类型：
--
作者：
Leenstra, T;Acosta, LP;Kurtis, JD
虽然血吸虫病是有效的治疗吡喹酮，快速再感染与反弹的发病率排除了有效的控制基础上的化疗，并证明目前的努力，为这些寄生虫的疫苗开发。采用纵向治疗-再感染研究设计，纳入616名7 - 30岁的受试者，我们评估了吡喹酮治疗4周后对日本血吸虫可溶性成虫提取物（SWAP）、Sj 97、Sj22.6和Sj 67的细胞因子应答与菲律宾莱特人群再感染抵抗力之间的关系。日本血吸虫是地方性的。S.日本血吸虫传播率高，6个月内再感染率为54.8%，18个月内再感染率为91.1%。以下细胞因子比率中的Th 2偏倚，白细胞介素-4（IL-4）/IL-12、IL-5/IL-12、IL-13/IL-12、IL-4/γ-IFN（IFN-γ）、IL-5/IFN-γ和IL-13/IFN-γ，SWAP组再感染时间延长1.4 ~ 2.9个月（P < 0.05），再感染强度降低27 ~ 55%（P < 0.05）。同样，对Sj 97应答的Th 2偏倚预测再感染时间延长1.6- 2.2个月（P < 0.05），再感染强度降低30%-41%（P < 0.05）。只有高的IL-5/IL-10比值对Sj22.6的应答预测了3.0个月的再感染时间（P = 0.03）。细胞因子对Sj 67的反应与保护无关。在一项大规模的人群治疗再感染研究中，我们发现对SWAP和Sj 97的Th 2应答一致地预测了对再感染的抵抗力。这些发现强调了Th 2型免疫应答在人类抵抗S.并支持Sj 97作为该寄生虫的主要候选疫苗。
Although schistosomiasis is effectively treated with Praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Using a longitudinal treatment-reinfection study design with 616 participants 7 to 30 years of age, we evaluated the relationship between cytokine responses to Schistosoma japonicum soluble adult worm extract (SWAP), Sj97, Sj22.6, and Sj67, measured 4 weeks after treatment with Praziquantel, and resistance to reinfection in a population from Leyte, The Philippines, where S. japonicum is endemic. S. japonicum transmission was high: 54.8% and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, interleukin-4 (IL-4)/IL-12, IL-5/IL-12, IL-13/IL-12, IL-4/gamma-IFN (IFN-gamma), IL-5/ IFN-gamma, and IL-13/IFN-gamma, in response to SWAP predicted a 1.4- to 2.9-month longer time to reinfection (P < 0.05) and a 27 to 55% lower intensity of reinfection (P < 0.05). Similarly, a Th2 bias in response to Sj97 predicted a 1.6- to 2.2-month longer time to reinfection (P < 0.05) and a 30 to 41% lower intensity of reinfection (P < 0.05). Only a high IL-5/IL-10 ratio in response to Sj22.6 predicted a 3.0-month-longer time to reinfection (P = 0.03). Cytokine responses to Sj67 were not associated with protection. In a large population-based treatment-reinfection study we found that Th2 responses to SWAP and Sj97 consistently predicted resistance to reinfection. These findings underscore Th2-type immune responses as central in human resistance to S. japonicum and support Sj97 as a leading vaccine candidate for this parasite.