Phase 1 vaccine trial of Pvs25H:: a transmission blocking vaccine for Plasmodium vivax malaria
Phase 1 vaccine trial of Pvs25H:: a transmission blocking vaccine for Plasmodium vivax malaria
复制标题
DOI：
10.1016/j.vaccine.2004.12.019
复制
发表时间：
2005-05-02
期刊：
影响因子：
5.5
通讯作者：
Saul, A
中科院分区：
文献类型：
--
作者：
Malkin, EM;Durbin, AP;Saul, A
间日疟原虫是非洲以外的大多数疟疾病例的原因，并导致大量发病。传播阻断疫苗是控制或消除疟疾的多方面公共卫生方法的一个潜在的有力组成部分。我们报告了间日疟原虫传播阻断疫苗在人类中的第一个1期临床试验。Pvs 25 H疫苗是来源于间日疟原虫动卵细胞的Pvs 25表面抗原的重组蛋白。该蛋白在酿酒酵母中表达，纯化，并吸附到Alhydrogel上。在一项开放标签研究中，3个剂量组（5、20或80 p，g）各10名志愿者在0、28和180天时通过肌内注射接种疫苗。未观察到与疫苗相关的严重不良事件。大多数与疫苗接种有因果关系的不良事件的严重程度为轻度或中度。注射部位压痛是最常见的不良事件。通过ELISA测量的抗Pvs 25 H抗体水平在第三次接种后达到峰值。疫苗诱导的抗体具有功能活性，如膜饲养试验中显著的传递阻断活性所证明。观察到抗体浓度与抑制程度之间的相关性。Pvs 25 H在人体中产生针对间日疟原虫的传播阻断免疫，证明了该抗原作为传播阻断疫苗组分的潜力。(c)2005爱思唯尔有限公司保留所有权利。
Plasmodium vivax is responsible for the majority of malaria cases outside of Africa, and results in substantial morbidity. Transmission blocking vaccines are a potentially powerful component of a multi-faceted public health approach to controlling or eliminating malaria. We report the first phase 1 clinical trial of a P. vivax transmission blocking vaccine in humans. The Pvs25H vaccine is a recombinant protein derived from the Pvs25 surface antigen of P. vivax ookinetes. The protein was expressed in Saccharomyces cerevisiae, purified, and adsorbed onto Alhydrogel. Ten volunteers in each of three dose groups (5, 20, or 80 p,g) were vaccinated by intramuscular injection in an open-label study at 0, 28 and 180 days. No vaccine-related serious adverse events were observed. The majority of adverse events causally related to vaccination were mild or moderate in severity. Injection site tenderness was the most commonly observed adverse event. Anti-Pvs25H antibody levels measured by ELISA peaked after the third vaccination. Vaccine-induced antibody is functionally active as evidenced by significant transmission blocking activity in the membrane feeding assay. Correlation between antibody concentration and degree of inhibition was observed. Pvs25H generates transmission blocking immunity in humans against P. vivax demonstrating the potential of this antigen as a component of a transmission blocking vaccine. (c) 2005 Elsevier Ltd. All rights reserved.