Ehrman Ryanne N, Brohlin Olivia R, Wijesundara Yalini H, Kumari Sneha, Trashi Orikeda, Howlett Thomas S, Trashi Ikeda, Herbert Fabian C, Raja Arun, Koirala Shailendra, Tran Nancy, Al-Kharji Noora M, Tang Wendy, Senarathna Milinda C, Hagge Laurel M, Smaldone Ronald A, Gassensmith Jeremiah J
Department of Chemistry and Biochemistry, The University of Texas at Dallas 800 West Campbell Rd. Richardson TX 75080 USA
Department of Biomedical Engineering, The University of Texas at Dallas 800 West Campbell Rd. Richardson TX 75080 USA.
Chem Sci. 2024 Jan 24;15(8):2731-2744. doi: 10.1039/d3sc06734c. eCollection 2024 Feb 22.
Vaccines have saved countless lives by preventing and even irradicating infectious diseases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immunogenicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vaccinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as opposed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phenomenon is at least partly owed to the metalloimmunological effects of the zinc metal as well as the sustained release of OVA from the ZIF-8 composite. The system acts as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the humoral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a laboratory setting, sufficient for up to 20 000 vaccine doses.
疫苗通过预防甚至根除传染病拯救了无数生命。常用的亚单位疫苗由从病原体中分离出的一种或多种重组蛋白组成，其安全性优于活疫苗或减毒疫苗。然而，这些疫苗的免疫原性较弱，因此，亚单位疫苗需要一系列剂量才能获得足够的针对病原体的免疫力。在此，我们表明，在沸石咪唑酯骨架-8（ZIF-8）中对惰性模型抗原卵清蛋白（OVA）进行仿生矿化，与三次推注剂量的OVA（OVA 3×）相比，能显著改善体液免疫反应。将OVA封装在ZIF-8中（OVA@ZIF）显示出比OVA 3×更高的针对OVA的血清抗体滴度。与OVA 3×相比，接种OVA@ZIF的小鼠生发中心（GC）B细胞和IgG1+ GC B细胞的数量更多，这表明发生了类别转换重组。我们表明，这种现象的机制至少部分归因于锌金属的金属免疫效应以及OVA从ZIF-8复合物中的持续释放。该系统作为抗原储存库，供抗原呈递细胞进入引流淋巴结，增强体液反应。最后，我们的模型系统OVA@ZIF在实验室环境中能以克级规模快速生产，足以制备多达20000剂疫苗。
