Plasmodium falciparum merozoite surface protein 1 as asexual blood stage malaria vaccine candidate

Malaria represents a public health challenge in tropical and subtropical regions, and currently deployed control strategies are likely insufficient to drive elimination of malaria. Development and improvement of malaria vaccines might be key to reduce disease burden. Vaccines targeting asexual blood stages of the parasite have shown limited efficacy when studied in human trials conducted over the past decades. Vaccine candidates based on the merozoite surface protein 1 (MSP1) were initially envisioned as one of the most promising approaches to provide immune protection against asexual blood-stage malaria. Successful immunization studies in monkey involved the use of the full-length MSP1 (MSP1FL) as vaccine construct. Vaccines using MSP1FL for immunization have the potential benefit of including numerous conserved B-cell and T-cell epitopes. This could result in improved parasite strain-transcending, protective immunity in the field. We review outcomes of clinical trials that utilized a variety of MSP1 constructs and formulations, including MSP1FL, either alone or in combination with other antigens, in both animal models and humans. Novel approaches to analyze breadth and magnitude of effector functions of MSP1-targeting antibodies in volunteers undergoing experimental vaccination and controlled human malaria infection will help to define correlates of protective immunity.

疟疾在热带与亚热带地区是一项严峻的公共卫生挑战，当前已部署的防控策略或许不足以实现疟疾消除目标。研发并优化疟疾疫苗，乃是降低疾病负担的关键所在。过往数十年来开展的人体临床试验显示，靶向疟原虫无性血液阶段的疫苗保护效力有限。基于裂殖子表面蛋白1（merozoite surface protein 1, MSP1）的候选疫苗，最初被视为提供针对无性血液阶段疟疾免疫保护的最具前景的策略之一。在非人灵长类动物中开展的成功免疫研究，采用全长MSP1（MSP1FL）作为疫苗构建体。采用MSP1FL进行免疫的疫苗，具备纳入大量保守B细胞与T细胞表位的潜在优势，有望在实际应用中提升跨疟原虫毒株的保护性免疫效果。本综述回顾了多种MSP1构建体与制剂（包括单独使用或与其他抗原联合使用的MSP1FL）在动物模型及人体中开展的临床试验结果。未来，针对接受实验性疫苗接种并接受受控人体疟疾感染的志愿者，分析其靶向MSP1的抗体效应功能的广度与强度的新型方法，将有助于明确保护性免疫的相关标志物。