Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy.

Sm-p80-based schistosomiasis vaccine: double-blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission-blocking efficacy.
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DOI:
10.1111/nyas.13942
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发表时间:
2018-08
影响因子:
5.2
通讯作者:
Siddiqui AA
Siddiqui AA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang W;Molehin AJ;Rojo JU;Sudduth J;Ganapathy PK;Kim E;Siddiqui AJ;Freeborn J;Sennoune SR;May J;Lazarus S;Nguyen C;Redman WK;Ahmad G;Torben W;Karmakar S;Le L;Kottapalli KR;Kottapalli P;Wolf RF;Papin JF;Carey D;Gray SA;Bergthold JD;Damian RT;Mayer BT;Marks F;Reed SG;Carter D;Siddiqui AA

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血吸虫病对79个国家约10亿人的公共卫生具有重要意义。急需疫苗。在这里,我们报告了四个独立的,双盲研究的结果,在狒狒的Sm-p80为基础的疫苗。与未接种疫苗的对照动物相比,该疫苗对曼氏血吸虫感染的传播表现出有效的预防效果,并且与显著较少的卵诱导的病理学相关。具体而言,该疫苗导致致病性雌蠕虫减少93.45%,并通过减少89.95%的组织卵载量,显著解决了肝/肠血吸虫病的主要临床表现。接种动物粪便虫卵排泄减少35倍,以及虫卵孵化至蜗牛感染期(毛蚴)减少81.51%,证明了疫苗阻断寄生虫传播的潜力。雌性蠕虫中Sm-p80的表达和接种疫苗的狒狒中Sm-p80特异性抗体的显著升高似乎在疫苗介导的保护中发挥重要作用。RNA测序的初步分析揭示了狒狒免疫效应细胞中疫苗诱导效应的不同分子特征。这项研究为基于Sm-p80的血吸虫病疫苗的有效性提供了全面的证据。血吸虫病对79个国家约10亿人的公共卫生具有重要意义。急需疫苗。在这里,我们报告了四个独立的,双盲研究的结果,在狒狒的Sm-p80为基础的疫苗。与未接种疫苗的对照动物相比,该疫苗对曼氏血吸虫感染的传播表现出有效的预防效果,并且与显著较少的卵诱导的病理学相关。
Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80–based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg–induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg–load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80–specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80–based vaccine for schistosomiasis. Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80–based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg–induced pathology, compared with unvaccinated control animals.
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