Inserm-Université Lille 2, Institut Pasteur de Lille, Lille, France.
PLoS Negl Trop Dis. 2012;6(7):e1704. doi: 10.1371/journal.pntd.0001704. Epub 2012 Jul 3.
Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) in healthy volunteers, and to determine its immunogenicity.
Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum) as adjuvant (n = 8), or Alum alone as a comparator (n = 8), twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8) received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production.
Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST.
rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that clinical trials with rSh28GST could be continued in humans as a potential vaccine candidate against urinary schistosomiasis.
由于快速再感染和可能对吡喹酮治疗的敏感性有限，化学疗法治疗尿路血吸虫病仍然具有挑战性。因此，治疗性疫苗代表了一种有吸引力的替代控制策略。本研究的目的是评估重组埃及血吸虫 28 kDa 谷胱甘肽 S-转移酶（rSh28GST）在健康志愿者中的安全性和耐受性，并确定其免疫原性。
志愿者随机接受 100 µg rSh28GST 与氢氧化铝（Alum）作为佐剂（n = 8），或单独接受 Alum 作为对照（n = 8），两次剂量间隔 28 天。这一组在第 150 天接受 rSh28GST 或单独 Alum 的第三剂。鉴于获得的结果，另一组健康志愿者（n = 8）再次接受两次 300 µg rSh28GST 的剂量，间隔 28 天。进行了为期六个月的随访，包括临床和生物学评估。疫苗候选物的免疫原性通过特异性抗体产生，血清抑制抗原酶活性的能力以及体外细胞因子产生来评估。
在 24 名健康男性参与者中，在给药后几天或几周内没有报告严重的不良事件。在接受 rSh28GST 的 4 名受试者中，报告了注射部位的轻度反应，而在 24 名受试者中有 8 名观察到胆红素的临床无意义增加。未检测到血液学或生化毒性证据。免疫分析表明 rSh28GST 具有免疫原性。诱导的 Th2 型反应的特征是能够抑制 rSh28GST 酶活性的抗体。
rSh28GST 与 Alum 一起在健康成年人中未引起任何明显的毒性，并产生了 Th2 型免疫反应。结合先前的临床前结果，安全性，耐受性和特异性免疫反应的质量数据提供了证据，表明可以在人类中继续进行 rSh28GST 的临床试验，作为治疗尿路血吸虫病的潜在疫苗候选物。
