Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, Salvador, Bahia, Brazil; Departamento de Biologia Geral do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Departamento de Biologia Celular do Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, Distrito Federal, Brazil.
Departamento de Bioquímica e Imunologia do Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), CNPq MCT, Salvador, Bahia, Brazil.
PLoS Negl Trop Dis. 2014 Mar 20;8(3):e2750. doi: 10.1371/journal.pntd.0002750. eCollection 2014 Mar.
The parasitic flatworm Schistosoma mansoni is a blood fluke that causes schistosomiasis. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Numerous antigens that are expressed at the interface between the parasite and the mammalian host have been assessed. Among the most promising molecules are the proteins present in the tegument and digestive tract of the parasite.
METHODOLOGY/PRINCIPAL FINDINGS: In this study, we evaluated the potential of Sm10.3, a member of the micro-exon gene 4 (MEG-4) family, for use as part of a recombinant vaccine. We confirmed by real-time PCR that Sm10.3 was expressed at all stages of the parasite life cycle. The localization of Sm10.3 on the surface and lumen of the esophageal and intestinal tract in adult worms and lung-stage schistosomula was confirmed by confocal microscopy. We also show preliminary evidence that rSm10.3 induces erythrocyte agglutination in vitro. Immunization of mice with rSm10.3 induced a mixed Th1/Th2-type response, as IFN-γ, TNF-α, and low levels of IL-5 were detected in the supernatant of cultured splenocytes. The protective effect conferred by vaccination with rSm10.3 was demonstrated by 25.5-32% reduction in the worm burden, 32.9-43.6% reduction in the number of eggs per gram of hepatic tissue, a 23.8% reduction in the number of granulomas, an 11.8% reduction in the area of the granulomas and a 39.8% reduction in granuloma fibrosis.
CONCLUSIONS/SIGNIFICANCE: Our data suggest that Sm10.3 is a potential candidate for use in developing a multi-antigen vaccine to control schistosomiasis and provide the first evidence for a possible role for Sm10.3 in the blood feeding process.
寄生扁形动物曼氏血吸虫是一种引起血吸虫病的血吸。当前的血吸虫病控制策略主要基于化学疗法,但许多研究人员认为,控制疾病的最佳长期策略是药物治疗与抗血吸虫疫苗免疫相结合。已经评估了许多在寄生虫与哺乳动物宿主之间的界面表达的抗原。最有前途的分子之一是寄生虫的表皮和消化道中存在的蛋白质。
方法/主要发现:在这项研究中,我们评估了 Sm10.3,即微外显子基因 4(MEG-4)家族的成员,作为重组疫苗的一部分的潜力。我们通过实时 PCR 证实 Sm10.3 在寄生虫生命周期的所有阶段都有表达。通过共聚焦显微镜证实 Sm10.3 在成虫和肺期童虫的食管和肠道的表面和腔中定位于表面和腔中。我们还初步证明 rSm10.3 在体外诱导红细胞凝集。用 rSm10.3 免疫小鼠可诱导混合 Th1/Th2 型反应,因为在培养的脾细胞上清液中检测到 IFN-γ、TNF-α 和低水平的 IL-5。用 rSm10.3 进行疫苗接种可减少 25.5-32%的虫体负荷、32.9-43.6%的每克肝组织中的卵数、23.8%的肉芽肿数减少、11.8%的肉芽肿面积减少和 39.8%的肉芽肿纤维化减少,从而证明了这种保护作用。
结论/意义:我们的数据表明 Sm10.3 是开发用于控制血吸虫病的多抗原疫苗的潜在候选物,并提供了 Sm10.3 可能在血液摄食过程中起作用的第一个证据。