Department of Biology and Biochemistry, University of Bath, Bath, UK.
Department of Chemistry, University of Bath, Bath, UK.
Sci Rep. 2019 Aug 8;9(1):11409. doi: 10.1038/s41598-019-47657-9.
There is an urgent need for the development of vaccine thermostabilisation methodologies as the maintenance of a continuous and reliable cold chain remains a major hurdle to the global distribution of safe and effective vaccines. Ensilication, a method that encases proteins in a resistant silica cage has been shown to physically prevent the thermal denaturation of a number of model proteins. In this study we investigate the utility of this promising approach in improving the thermal stability of antigens and vaccine conjugates highly relevant to the development of candidate tuberculosis vaccines, including antigen 85b conjugated with the Staphylococcus aureus-protein based adjuvant Sbi. Here we analyse the sensitivity of these constructs to thermal denaturation and demonstrate for the first time the benefits of ensilication in conferring these vaccine-relevant proteins with protection against temperature-induced loss of structure and function without the need for refrigeration. Our results reveal the potential of ensilication in facilitating the storage and transport of vaccines at ambient temperatures in the future and therefore in delivering life-saving vaccines globally, and in particular to remote areas of developing countries where disease rates are often highest.
目前迫切需要开发疫苗热稳定化方法，因为保持持续可靠的冷链仍然是安全有效疫苗在全球分发的主要障碍。包埋法是一种将蛋白质封装在耐硅胶笼中的方法，已被证明可以物理阻止许多模型蛋白质的热变性。在这项研究中，我们研究了这种有前途的方法在提高与候选结核病疫苗开发相关的抗原和疫苗缀合物的热稳定性方面的效用，包括与金黄色葡萄球菌蛋白基础佐剂 Sbi 缀合的抗原 85b。在这里，我们分析了这些结构对热变性的敏感性，并首次证明了包埋法的益处，它可以使这些与疫苗相关的蛋白质在不需要冷藏的情况下，免受温度诱导的结构和功能丧失的影响。我们的研究结果揭示了包埋法在未来促进疫苗在环境温度下储存和运输的潜力，从而在全球范围内提供救命疫苗，特别是在疾病发生率通常最高的发展中国家的偏远地区。
