Leenstra Tjalling, Acosta Luz P, Wu Hai-Wei, Langdon Gretchen C, Solomon Julie S, Manalo Daria L, Su Li, Jiz Mario, Jarilla Blanca, Pablo Archie O, McGarvey Stephen T, Olveda Remigio M, Friedman Jennifer F, Kurtis Jonathan D
Center for International Health Research, Brown University Medical School, 55 Claverick St., Providence, RI 02903, USA.
Infect Immun. 2006 Jan;74(1):370-81. doi: 10.1128/IAI.74.1.370-381.2006.
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.
虽然吡喹酮能有效治疗血吸虫病，但快速再感染及由此引发的发病率反弹使得仅依靠化疗无法有效控制血吸虫病，这也为目前研发针对这些寄生虫的疫苗的努力提供了正当理由。我们采用纵向治疗-再感染研究设计，对616名7至30岁的参与者进行了研究，评估了在菲律宾莱特省（日本血吸虫的流行地区），吡喹酮治疗4周后对日本血吸虫可溶性成虫提取物（SWAP）、Sj97、Sj22.6和Sj67的细胞因子反应与再感染抵抗力之间的关系。日本血吸虫的传播率很高：分别有54.8%和91.1%的人在6个月和18个月内再次感染。对SWAP的以下细胞因子比率（白细胞介素-4（IL-4）/白细胞介素-12、IL-5/IL-12、IL-13/IL-12、IL-4/γ-干扰素（IFN-γ）、IL-5/IFN-γ和IL-13/IFN-γ）呈现Th2偏向，预示着再感染时间延长1.4至2.9个月（P < 0.05），再感染强度降低27%至55%（P < 0.05）。同样，对Sj97的Th2偏向预示着再感染时间延长1.6至2.2个月（P < 0.05），再感染强度降低30%至41%（P < 0.05）。仅对Sj22.6的高IL-5/IL-10比率预示着再感染时间延长3.0个月（P = 0.03）。对Sj67的细胞因子反应与保护作用无关。在一项基于大规模人群的治疗-再感染研究中，我们发现对SWAP和Sj97的Th2反应始终预示着对再感染的抵抗力。这些发现强调了Th2型免疫反应在人类抵抗日本血吸虫中的核心作用，并支持Sj97作为该寄生虫的主要疫苗候选物。
