Molehin Adebayo J, Sennoune Souad R, Zhang Weidong, Rojo Juan U, Siddiqui Arif J, Herrera Karlie A, Johnson Laura, Sudduth Justin, May Jordan, Siddiqui Afzal A
Center for Tropical Medicine and Infectious Diseases, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Parasitol Res. 2017 Nov;116(11):3175-3188. doi: 10.1007/s00436-017-5634-4. Epub 2017 Oct 12.
Schistosomiasis remains a major global health problem. Despite large-scale schistosomiasis control efforts, clear limitations such as possible emergence of drug resistance and reinfection rates highlight the need for an effective schistosomiasis vaccine. Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine formulations have shown remarkable efficacy in protecting against S. mansoni challenge infections in mice and baboons. In this study, we evaluated the cross-species protective efficacy of Sm-p80 vaccine against S. japonicum and S. haematobium challenge infections in rodent models. We also elucidated the expression of Sm-p80 and Sm-p80 ortholog proteins in different developmental stages of S. mansoni, S. haematobium, and S. japonicum. Immunization with Sm-p80 vaccine reduced worm burden by 46.75% against S. japonicum challenge infection in mice. DNA prime/protein boost (1 + 1 dose administered on a single day) resulted in 26.95% reduction in worm burden in S. haematobium-hamster infection/challenge model. A balanced Th1 (IFN-γ, TNF-α, IL-2, and IL-12) and Th2 (IL-4, IgG1) type of responses were observed following vaccination in both S. japonicum and S. haematobium challenge trials and these are associated with the prophylactic efficacy of Sm-p80 vaccine. Immunohistochemistry demonstrated that Sm-p80/Sm-p80 ortholog proteins are expressed in different life cycle stages of the three major human species of schistosomes studied. The data presented in this study reinforce the potential of Sm-p80-based vaccine for both hepatic/intestinal and urogenital schistosomiasis occurring in different geographical areas of the world. Differential expression of Sm-p80/Sm-p80 protein orthologs in different life cycle makes this vaccine potentially useful in targeting different levels of infection, disease, and transmission.
血吸虫病仍然是一个重大的全球健康问题。尽管开展了大规模的血吸虫病防治工作，但诸如可能出现耐药性和再感染率等明显局限性凸显了开发有效血吸虫病疫苗的必要性。基于曼氏血吸虫钙蛋白酶大亚基（Sm-p80）的疫苗制剂在保护小鼠和狒狒免受曼氏血吸虫攻击感染方面已显示出显著疗效。在本研究中，我们评估了Sm-p80疫苗在啮齿动物模型中对日本血吸虫和埃及血吸虫攻击感染的跨物种保护效力。我们还阐明了Sm-p80和Sm-p80直系同源蛋白在曼氏血吸虫、埃及血吸虫和日本血吸虫不同发育阶段的表达情况。用Sm-p80疫苗免疫可使小鼠抵抗日本血吸虫攻击感染的虫负荷降低46.75%。DNA初免/蛋白加强免疫（在同一天给予1 + 1剂量）使埃及血吸虫-仓鼠感染/攻击模型中的虫负荷降低了26.95%。在日本血吸虫和埃及血吸虫攻击试验中，接种疫苗后均观察到了平衡的Th1（IFN-γ、TNF-α、IL-2和IL-12）和Th2（IL-4、IgG1）型反应，这些反应与Sm-p80疫苗的预防效力相关。免疫组织化学表明，Sm-p80/Sm-p80直系同源蛋白在所研究的三种主要人体血吸虫的不同生命周期阶段均有表达。本研究提供的数据强化了基于Sm-p80的疫苗对世界不同地理区域发生的肝/肠型和泌尿生殖型血吸虫病的潜力。Sm-p80/Sm-p80蛋白直系同源物在不同生命周期中的差异表达使这种疫苗有可能用于针对不同程度的感染、疾病和传播。
