Wang Lu, Ramirez Aaron, Felgner Jiin, Li Enya, Hernandez-Davies Jenny E, Gregory Anthony E, Felgner Philip L, Mohraz Ali, Davies D Huw, Wang Szu-Wen
Department of Chemical and Biomolecular Engineering, University of California, Irvine, CA, USA.
Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, CA, USA.
Drug Deliv. 2025 Dec;32(1):2476144. doi: 10.1080/10717544.2025.2476144. Epub 2025 May 2.
Q fever is a zoonotic infectious disease caused by and there is currently no FDA-approved vaccine for human use. The whole-cell inactivated vaccine Q-VAX, which is only licensed in Australia, has a risk of causing severe adverse reactions, making subunit vaccines a good alternative. However, most subunit antigens are weak immunogens and require two or more immunizations to elicit an adequate level of immunity. We hypothesized that by combining a nanoparticle to co-deliver both a protein antigen and an adjuvant, together with a hydrogel depot for sustained-release kinetics, a single-administration of a nanoparticle-loaded hydrogel vaccine could elicit a strong and durable immune response. We synthesized and characterized a protein nanoparticle (CBU-CpG-E2) that co-delivered the immunodominant protein antigen CBU1910 (CBU) from and the adjuvant CpG1826 (CpG). For sustained release, we examined different mixtures of PLGA-PEG-PLGA (PPP) polymers and identified a PPP solution that was injectable at room temperature, formed a hydrogel at physiological temperature, and continuously released protein for 8 weeks . Single-dose vaccine formulations were administered to mice, and IgG, IgG1, and IgG2c levels were determined over time. The vaccine combining both the CBU-CpG-E2 nanoparticles and the PPP hydrogel elicited a stronger and more durable humoral immune response than the soluble bolus nanoparticle vaccines (without hydrogel) and the free antigen and free adjuvant-loaded hydrogel vaccines (without nanoparticles), and it yielded a balanced IgG2c/IgG1 response. This study demonstrates the potential advantages of using this modular PPP hydrogel/nanoparticle system to elicit improved immune responses against infectious pathogens.
Q热是一种由[病原体名称未给出]引起的人畜共患传染病，目前尚无美国食品药品监督管理局（FDA）批准的用于人类的疫苗。全细胞灭活疫苗Q-VAX仅在澳大利亚获得许可，有引起严重不良反应的风险，这使得亚单位疫苗成为一个不错的选择。然而，大多数亚单位抗原是弱免疫原，需要两次或更多次免疫才能引发足够水平的免疫力。我们假设，通过结合一种纳米颗粒来共同递送蛋白质抗原和佐剂，并结合一种用于缓释动力学的水凝胶贮库，单次注射负载纳米颗粒的水凝胶疫苗可以引发强烈而持久的免疫反应。我们合成并表征了一种蛋白质纳米颗粒（CBU-CpG-E2），它共同递送来自[病原体名称未给出]的免疫显性蛋白质抗原CBU1910（CBU）和佐剂CpG1826（CpG）。为了实现持续释放，我们研究了聚乳酸-聚乙二醇-聚乳酸（PPP）聚合物的不同混合物，并确定了一种在室温下可注射、在生理温度下形成水凝胶并能持续释放蛋白质8周的PPP溶液。将单剂量疫苗制剂注射到小鼠体内，并随时间测定IgG、IgG1和IgG2c水平。与可溶性大剂量纳米颗粒疫苗（无水凝胶）以及负载游离抗原和游离佐剂的水凝胶疫苗（无纳米颗粒）相比，结合了CBU-CpG-E2纳米颗粒和PPP水凝胶的疫苗引发了更强、更持久的体液免疫反应，并且产生了平衡的IgG2c/IgG1反应。这项研究证明了使用这种模块化的PPP水凝胶/纳米颗粒系统来引发针对感染性病原体的更好免疫反应的潜在优势。
