Maheshwari Anshika, Dookie Rebecca, Gaytán Meztlli O, Henriques-Normark Birgitta, Sotiriou Georgios A
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden.
Clinical Microbiology, Karolinska University Hospital, Stockholm 171 77, Sweden.
ACS Appl Nano Mater. 2025 May 27;8(23):11986-11996. doi: 10.1021/acsanm.5c01535. eCollection 2025 Jun 13.
The use of nanoparticles in vaccine formulations has become increasingly prevalent, with the rise of subunit vaccines. However, the production of nanoparticles is often not scalable, presenting a significant challenge for large-scale vaccine manufacturing. Additionally, these nanoparticle delivery systems often require additional immunopotentiators to elicit a robust immune response, further complicating vaccine formulation. In this study, we explore the potential of flame-synthesized calcium phosphate (CaP) nanoparticles, produced via flame spray pyrolysis (FSP) (a highly reproducible and scalable method), as vaccine adjuvants capable of both antigen delivery and immunostimulation. We produced three different CaP nanoparticles with controlled crystallinity and size to screen for their immunostimulatory properties and evaluated their capacity to load and protect the model antigen ovalbumin (OVA) from enzymatic degradation. Our results show that all three CaP nanoparticles significantly enhance antigen internalization and processing by bone marrow-derived dendritic cells (BMDCs), critical for effective T cell activation. OVA conjugated with amorphous CaP nanoparticles outperformed crystalline CaP in increasing the expression of costimulatory markers CD86 and CD80 on BMDCs, as well as enhancing IL-6 production, indicating their potential as effective immunopotentiators. This dual functionality, in addition to the facile synthesis process, could simplify vaccine formulations by obviating the need for separate immunostimulatory agents. This work lays the foundation for further research to establish the flame-made CaP nanoparticle effectiveness and safety as adjuvants .
随着亚单位疫苗的兴起，纳米颗粒在疫苗制剂中的应用越来越普遍。然而，纳米颗粒的生产往往难以扩大规模，这对大规模疫苗生产构成了重大挑战。此外，这些纳米颗粒递送系统通常需要额外的免疫增强剂来引发强烈的免疫反应，这进一步使疫苗配方复杂化。在本研究中，我们探索了通过火焰喷雾热解（FSP，一种高度可重复且可扩展的方法）制备的火焰合成磷酸钙（CaP）纳米颗粒作为能够同时递送抗原和刺激免疫的疫苗佐剂的潜力。我们制备了三种具有可控结晶度和尺寸的不同CaP纳米颗粒，以筛选它们的免疫刺激特性，并评估它们负载和保护模型抗原卵清蛋白（OVA）免受酶降解的能力。我们的结果表明，所有三种CaP纳米颗粒均能显著增强骨髓来源的树突状细胞（BMDC）对抗原的内化和加工，这对有效的T细胞激活至关重要。与无定形CaP纳米颗粒偶联的OVA在增加BMDC上共刺激分子CD86和CD80的表达以及增强IL-6产生方面优于结晶CaP，表明它们作为有效免疫增强剂的潜力。这种双重功能，再加上简便的合成过程，无需单独的免疫刺激剂，从而可以简化疫苗配方。这项工作为进一步研究奠定了基础，以确定火焰制备的CaP纳米颗粒作为佐剂的有效性和安全性。
