Laboratório de Biologia e Imunologia de Doenças Infeciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil.
Laboratório de Esquistossomose, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil.
Front Immunol. 2018 Nov 2;9:2488. doi: 10.3389/fimmu.2018.02488. eCollection 2018.
The helminth is one of main causes of human schistosomiasis, a health and economic concern in some of the world's poorest countries. Current treatment regimens can lead to serious side effects and are not suitable for breastfeeding mothers. As such, efforts have been undertaken to develop a vaccine to prevent infection. Of these, Sm29 is a promising candidate that has been associated with resistance to infection/reinfection in humans and mice. Its ability to induce resistance to reinfection has also been recently demonstrated using a vaccine formulation containing Freund's adjuvant. However, Freund's adjuvant is unsuitable for use in human vaccines. We therefore evaluated the ability of Sm29 to induce protection against reinfection when formulated with either alum or MPLA as an adjuvant, both approved for human use. Our data demonstrate that, in contrast to Sm29 with MPLA, Sm29 with alum reduced parasite burden after reinfection compared to a control. We next investigated whether the immune response was involved in creating the differences between the protective (Sm29Alum) and non-protective (Sm29MPLA) vaccine formulations. We observed that both formulations induced a similar mixed-profile immune response, however, the Sm29 with alum formulation raised the levels of antibodies against Sm29. This suggests that there is an association between a reduction in worm burden and parasite-specific antibodies. In summary, our data show that Sm29 with an alum adjuvant can successfully protect against reinfection in mice, indicating a potentially effective vaccine formulation that could be applied in humans.
寄生虫是人类血吸虫病的主要病因之一,这种疾病在世界上一些最贫穷的国家是一个健康和经济方面的关注问题。目前的治疗方案可能会导致严重的副作用,并不适合哺乳期妇女。因此,人们一直在努力开发一种疫苗来预防感染。其中,Sm29 是一种很有前途的候选疫苗,它已被证明与人类和小鼠的抗感染/再感染能力有关。最近,使用含有弗氏佐剂的疫苗制剂也证明了它具有抵抗再感染的能力。然而,弗氏佐剂不适合用于人类疫苗。因此,我们评估了 Sm29 与铝佐剂或 MPLA 佐剂联合使用时诱导对再感染的保护能力,这两种佐剂都已被批准用于人类。我们的数据表明,与 MPLA 佐剂的 Sm29 相反,与铝佐剂的 Sm29 在再感染后可降低寄生虫负荷。我们接下来研究了免疫反应是否参与了产生保护性(Sm29Alum)和非保护性(Sm29MPLA)疫苗制剂之间的差异。我们观察到,两种制剂都诱导了相似的混合免疫反应,但铝佐剂的 Sm29 制剂提高了针对 Sm29 的抗体水平。这表明在蠕虫负荷减少和寄生虫特异性抗体之间存在关联。总之,我们的数据表明,铝佐剂的 Sm29 可以成功地预防小鼠的再感染,表明这是一种潜在有效的疫苗制剂,可应用于人类。