Recent advances in recombinant protein-based malaria vaccines.
Recent advances in recombinant protein-based malaria vaccines.
复制标题
DOI：
10.1016/j.vaccine.2015.09.093
复制
发表时间：
2015-12-22
期刊：
影响因子：
5.5
通讯作者：
Biswas S
中科院分区：
文献类型：
--
作者：
Draper SJ;Angov E;Horii T;Miller LH;Srinivasan P;Theisen M;Biswas S
基于蛋白质的疫苗仍然是针对主要靶疟疾抗原的B细胞和抗体诱导的基础方法。抗原选择、免疫原设计和表位聚焦的进展正在推动该领域的发展。新的异源表达平台使下一代蛋白疫苗的cGMP生产成为可能。下一代抗原、基于蛋白质的免疫原和病毒样颗粒（VLP）递送平台正在临床开发中。基于蛋白质的疫苗将构成抗疟疾的高效多组分/多阶段/多抗原亚单位制剂的一部分。疟原虫寄生虫是人类疟疾的病原体，研制一种防止感染、疾病和传播的高效疫苗仍然是一个关键的优先事项。广泛确定的是，寄生虫在人类宿主和蚊子载体内的复杂生命周期的多个阶段对疫苗诱导的抗体敏感。通过亚单位疫苗接种诱导抗体的主要方法是递送配制在佐剂中的蛋白质抗原。在疟疾疫苗开发方面，特别是在靶抗原发现、蛋白质表达平台、佐剂测试和可溶性和病毒样颗粒（VLP）递送平台的开发方面，已经在这奋进做出了广泛的努力。随着下一代亚基设计中创新概念的探索，基于蛋白质的疫苗方法的广度正在继续扩大，开发高效多组分/多阶段/多抗原制剂的前景似乎越来越有可能。本文将重点介绍近年来针对疟原虫子孢子、裂殖子和有性阶段的主要疟疾抗原PfCelTOS、PfMSP 1、PfAMA 1、PfRH 5、PfSERA 5、PfGLURP、PfMSP 3、Pfs 48/45和Pfs 25的蛋白疫苗设计、开发和/或临床试验的进展。未来的前景和挑战的开发，生产，人类交付和评估的蛋白质为基础的疟疾疫苗进行了讨论。
Protein-based vaccines remain the cornerstone approach for B cell and antibody induction against leading target malaria antigens. Advances in antigen selection, immunogen design and epitope-focusing are advancing the field. New heterologous expression platforms are enabling cGMP production of next-generation protein vaccines. Next-generation antigens, protein-based immunogens and virus-like particle (VLP) delivery platforms are in clinical development. Protein-based vaccines will form part of a highly effective multi-component/multi-stage/multi-antigen subunit formulation against malaria. Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle–including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed.