Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA.
Agave BioSystems, Ithaca, NY 14850, USA.
Vaccine. 2022 Jul 29;40(31):4270-4280. doi: 10.1016/j.vaccine.2022.05.076. Epub 2022 Jun 10.
Despite the development of prophylactic anti-malarial drugs and practices to prevent infection, malaria remains a health concern. Preclinical testing of novel malaria vaccine strategies achieved through rational antigen selection and novel particle-based delivery platforms is yielding encouraging results. One such platform, self-assembling virus-like particles (VLP) is safer than attenuated live viruses, and has been approved as a vaccination tool by the FDA. We explore the use of Norovirus sub-viral particles lacking the natural shell (S) domain forming the interior shell but that retain the protruding (P) structures of the native virus as a vaccine vector. Epitope selection and their surface display has the potential to focus antigen specific immune responses to crucial epitopes. Recombinant P-particles displaying epitopes from two malaria antigens, Plasmodium falciparum (Pf) CelTOS and Plasmodium falciparum (Pf) CSP, were evaluated for immunogenicity and their ability to confer protection in a murine challenge model. Immune responses induced in mice resulted either in sterile protection (displaying PfCelTOS epitopes) or in antibodies with functional activity against sporozoites (displaying PfCSP epitopes) in an in vitro liver-stage development assay (ILSDA). These results are encouraging and support further evaluation of this platform as a vaccine delivery system.
尽管已经开发出预防性抗疟药物和预防感染的措施，但疟疾仍然是一个健康问题。通过合理的抗原选择和新型基于颗粒的递药平台进行的新型疟疾疫苗策略的临床前测试正在取得令人鼓舞的结果。其中一种平台是自组装病毒样颗粒（VLP），它比减毒活病毒更安全，已被 FDA 批准作为一种疫苗工具。我们探讨了使用缺乏天然外壳（S）结构域的诺如病毒亚病毒颗粒（S 结构域形成内部壳，但保留天然病毒的突出（P）结构）作为疫苗载体。表位选择及其表面展示有可能将抗原特异性免疫反应集中在关键表位上。展示来自两种疟疾抗原的表位的重组 P 颗粒，即疟原虫（Pf）CelTOS 和疟原虫（Pf）CSP，在小鼠挑战模型中评估了其免疫原性和保护能力。在小鼠中诱导的免疫反应导致无菌保护（显示 PfCelTOS 表位）或在体外肝脏阶段发育测定（ILSDA）中对孢子虫具有功能活性的抗体（显示 PfCSP 表位）。这些结果令人鼓舞，支持进一步评估该平台作为疫苗递送系统。
