Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, USA.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Int J Pharm. 2021 Jan 25;593:120168. doi: 10.1016/j.ijpharm.2020.120168. Epub 2020 Dec 10.
Malaria remains a global health threat, with significant morbidity and mortality worldwide despite current interventions. The human disease is caused by five different parasitic species, with Plasmodium falciparum being the deadliest. As a result, vaccine research against P. falciparum is a global priority. Merozoite surface protein 2 (MSP2) is a promising vaccine antigen as MSP2-specific antibodies have been shown previously to be protective against malaria infection. In this study, the formulation of an MSP2 vaccine was explored to enhance antigen uptake and achieve both an antibody and Th1 immune response by adsorbing MSP2 antigen onto a biomaterial carrier system. Specifically, MSP2 antigen was adsorbed onto acetalated dextran (Ace-DEX) microparticles (MPs). IgG and IgG2a titers elicited by the Ace-DEX MP platform were compared to titer levels elicited by MSP2 adsorbed to an FDA-approved alum adjuvant, MSP2 alone, and PBS alone. Both adsorption of MSP2 to Ace-DEX MPs and to alum elicited antibody responses in vivo, but only the formulation containing Ace-DEX MPs was able to elicit a significant Th1-biased response needed to combat the intracellular pathogen. As such, MSP2 adsorbed to Ace-DEX MPs demonstrates promise as a malaria vaccine.
疟疾仍然是全球健康威胁,尽管目前有干预措施,但全球仍有大量发病率和死亡率。人类疾病由五种不同的寄生虫种引起,其中恶性疟原虫最为致命。因此,针对恶性疟原虫的疫苗研究是全球的优先事项。裂殖子表面蛋白 2 (MSP2) 是一种很有前途的疫苗抗原,因为之前已经证明 MSP2 特异性抗体对疟疾感染具有保护作用。在这项研究中,通过将 MSP2 抗原吸附到生物材料载体系统上,探索了 MSP2 疫苗的配方,以增强抗原摄取并实现抗体和 Th1 免疫反应。具体来说,将 MSP2 抗原吸附到乙酰化葡聚糖 (Ace-DEX) 微球 (MPs) 上。将 Ace-DEX MP 平台引发的 IgG 和 IgG2a 滴度与吸附到 FDA 批准的明矾佐剂上的 MSP2、单独的 MSP2 和单独的 PBS 引发的滴度水平进行了比较。MSP2 吸附到 Ace-DEX MPs 和明矾都能在体内引发抗体反应,但只有含有 Ace-DEX MPs 的配方才能引发对抗细胞内病原体所需的显著 Th1 偏向反应。因此,吸附到 Ace-DEX MPs 的 MSP2 作为疟疾疫苗具有潜力。