Data from: Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults

Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) plays a role in the digestion of host hemoglobin by adult N. americanus hookworms. Vaccination of laboratory animals with recombinant Na-GST-1 is associated with significant protection from challenge infection. Recombinant Na-GST-1 was expressed in Pichia pastoris and adsorbed to aluminum hydroxide adjuvant (Alhydrogel) according to current Good Manufacturing Practice. Two Phase 1 trials were conducted in 142 healthy adult volunteers in the United States and Brazil, first in hookworm-naïve individuals and then in residents of a N. americanus endemic area in Brazil. Volunteers received one of three doses of recombinant Na-GST-1 (10, 30, or 100 μg) adjuvanted with Alhydrogel, adjuvanted with Alhydrogel and co-administered with an aqueous formulation of Glucopyranosyl Lipid A (GLA-AF), or the hepatitis B vaccine. Vaccinations were administered via intramuscular injection on days 0, 56, and 112. Na-GST-1/Alhydrogel was well tolerated in both hookworm-naïve and hookworm-exposed adults, with the most common adverse events being mild to moderate injection site pain and tenderness, and mild headache and nausea; no vaccine-related severe or serious adverse events were observed. Antigen-specific IgG antibodies were induced in a dose-dependent fashion, with increasing levels observed after each vaccination in both trials. The addition of GLA-AF to Na-GST-1/Alhydrogel did not result in significant increases in specific IgG responses. In both the US and Brazil studies, the predominant IgG subclass induced against Na-GST-1 was IgG1, with lesser amounts of IgG3. Vaccination of both hookworm-naïve and hookworm-exposed adults with recombinant Na-GST-1 was safe, well tolerated, and resulted in significant antigen-specific IgG responses. Based on these results, this vaccine will be advanced into clinical trials in children and eventual efficacy studies.

美洲板口线虫谷胱甘肽S-转移酶1（Glutathione-S-Transferase-1，简称Na-GST-1）在美洲板口线虫成虫消化宿主血红蛋白的过程中发挥关键作用。使用重组Na-GST-1免疫实验动物，可使其获得针对攻毒感染的显著保护效力。重组Na-GST-1在毕赤酵母（Pichia pastoris）中表达，并按照现行药品生产质量管理规范吸附于氢氧化铝佐剂（Alhydrogel）。研究团队在美国与巴西共纳入142名健康成年志愿者，开展了两项1期临床试验：首先针对钩虫未感染人群，随后针对巴西美洲板口线虫流行区的常住居民。志愿者被随机分配接受以下三种干预方案之一：三种剂量（10、30或100μg）的Alhydrogel佐剂重组Na-GST-1；Alhydrogel佐剂联合葡萄糖基脂质A水相制剂（GLA-AF）的重组Na-GST-1；或乙型肝炎疫苗。免疫接种均于第0、56、112天通过肌内注射完成。在钩虫未感染及既往感染的成年志愿者中，Na-GST-1/Alhydrogel均具有良好的耐受性，最常见的不良反应为轻至中度的注射部位疼痛与压痛，以及轻度头痛、恶心；未观察到与疫苗相关的严重或危及生命的不良事件。两项试验中，抗原特异性IgG抗体均呈剂量依赖性诱导产生，且每次免疫接种后抗体水平均有所升高。在Na-GST-1/Alhydrogel配方中加入GLA-AF，并未使特异性IgG应答出现显著提升。在美国与巴西的两项研究中，针对Na-GST-1诱导产生的主要IgG亚类为IgG1，IgG3的水平相对较低。对钩虫未感染及既往感染的成年志愿者接种重组Na-GST-1，具有良好的安全性与耐受性，且可诱导产生显著的抗原特异性IgG应答。基于上述研究结果，该疫苗将推进至儿童人群临床试验及最终的有效性研究阶段。