Mallory Katherine L, Taylor Justin A, Zou Xiaoyan, Waghela Ishita N, Schneider Cosette G, Sibilo Michael Q, Punde Neeraja M, Perazzo Leah C, Savransky Tatyana, Sedegah Martha, Dutta Sheetij, Janse Chris J, Pardi Norbert, Lin Paulo J C, Tam Ying K, Weissman Drew, Angov Evelina
Walter Reed Army Institute of Research, Silver Spring, MD, USA.
Parsons Corporation, Centreville, VA, USA.
NPJ Vaccines. 2021 Jun 18;6(1):84. doi: 10.1038/s41541-021-00345-0.
Human malaria affects the vast majority of the world's population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research. As the immunodominant coat protein of the invasive stage of the malaria parasite, circumsporozoite protein (PfCSP) was selected as the antigen of choice to assess the immunogenic and protective potential of an mRNA malaria vaccine. In mammalian cell transfection experiments, PfCSP mRNA was well expressed and cell associated. In the transition to an in vivo murine model, lipid nanoparticle (LNP) encapsulation was applied to protect and deliver the mRNA to the cell translation machinery and supply adjuvant activity. The immunogenic effect of an array of factors was explored, such as formulation, dose, number, and interval of immunizations. PfCSP mRNA-LNP achieved sterile protection against infection with two P. berghei PfCSP transgenic parasite strains, with mRNA dose and vaccination interval having a greater effect on outcome. This investigation serves as the assessment of pre-erythrocytic malaria, PfCSP mRNA vaccine candidate resulting in sterile protection, with numerous factors affecting protective efficacy, making it a compelling candidate for further investigation.
人类疟疾影响着世界上绝大多数人口，其中恶性疟原虫导致的发病率和死亡率最高。由于没有获得许可的疫苗，且主要候选疫苗在实际应用中提供的保护效果欠佳，因此对一种有效的免疫预防方法的需求持续推动疟疾研究界探索其他技术。信使核糖核酸（mRNA）领域的最新进展已将这个长期被忽视的平台提升到传染病研究的前沿。作为疟原虫侵入阶段的免疫显性表面蛋白，环子孢子蛋白（PfCSP）被选为评估mRNA疟疾疫苗免疫原性和保护潜力的首选抗原。在哺乳动物细胞转染实验中，PfCSP mRNA表达良好且与细胞相关。在向体内小鼠模型过渡时，应用脂质纳米颗粒（LNP）进行封装，以保护mRNA并将其递送至细胞翻译机制，同时提供佐剂活性。研究了一系列因素的免疫原性效应，如制剂、剂量、免疫次数和免疫间隔。PfCSP mRNA-LNP对两种伯氏疟原虫PfCSP转基因寄生虫株的感染实现了无菌保护，mRNA剂量和疫苗接种间隔对结果的影响更大。这项研究是对红细胞前期疟疾的评估，PfCSP mRNA疫苗候选物可导致无菌保护，有许多因素影响保护效果，使其成为进一步研究的有力候选物。
