Ionic liquid proteins: a route towards room temperature stable antibodies and vaccines

每年有1亿多婴儿接种疫苗，每年挽救300万人的生命。全球卫生界已认识到疫苗在预防疾病方面的重要性，并致力于在全球范围内提供疫苗。疾病控制及预防中心建议，除口服小儿麻痹症疫苗外，大部分疫苗应贮存于摄氏2至8度，以维持疫苗效力。但是，如果储存温度低于推荐的温度范围，那么疫苗的意外冷冻可能会导致结块，从而降低疫苗的效力。冷链实践往往忽视疫苗的意外冷冻，因为在较高温度下会产生相关的热损伤。尽管如此，儿童基金会2005年用于所有疫苗的4.39亿美元中，31%以上用于对冷冻敏感的疫苗。因此，向电力和冷藏有限的第三世界国家分发疫苗，给本已脆弱的“冷链”带来了额外的压力。治疗性蛋白质的储存的一种建议的解决方案是使用离子液体（IL）来增加蛋白质和抗体的热稳定性，从而避免在运输和储存期间对疫苗的冷藏的需要。离子液体由于其独特的、可调的性质，在材料科学、催化和药物化学等领域得到了广泛的应用。离子液体具有很高的热稳定性、化学稳定性和电化学稳定性。此外，对离子液体的大部分兴趣是由于它们的可忽略的蒸气压，因此可能是“绿色溶剂”来代替挥发性有机溶剂。尽管有这些优点，蛋白质在无水条件下往往是高度不稳定的，并且在离子液体中溶解性差。本研究提出使用抗体和病毒的表面修饰来增加它们在离子液体中的溶解度，增加蛋白质的热稳定性，同时保留它们的蛋白质生物学功能。

Vaccines are administered to more than 100 million infants a year, saving three million lives annually. The global health community has recognised the importance of vaccines in the prevention of diseases and are committed to making vaccines available globally. The Centres for Disease Control and Prevention (CDC) recommends that most vaccines should be stored between 2 and 8 Degrees Centigrade, except the oral polio vaccine, to maintain the vaccine efficacy. However, if the storage temperature is lower than the recommended temperature range, then accidental freezing of vaccines can lead to agglomeration, which can reduce the potency of vaccine. Cold chain practices tend to overlook accidental freezing of vaccines because of the associated heat damage at higher temperatures. Despite this, over 31 % of the US$ 439 million UNICEF spent on all vaccines in 2005 are spent on freeze-sensitive vaccines. Therefore, the distribution of vaccines to third-world countries, where electricity and cold storage are limited, puts additional stress on the already fragile 'cold chain'. A proposed solution to the storage of therapeutic proteins is to increase the thermal stability of proteins and antibodies using ionic liquids (ILs), avoiding the need for refrigeration of vaccines during shipping and storage. The use of ionic liquids have become increasingly popular and have been used for various applications such as material science, catalysis and medicinal chemistry due to their unique and tuneable properties. Ionic liquids have high thermal, chemical and electrochemical stabilities. In addition, most of the interest in ionic liquids is due to their negligible vapour pressures and therefore the possibility of a 'green solvent' to replace volatile organic solvents. Despite these advantages, proteins tend to be highly unstable in anhydrous conditions and poorly soluble in ionic liquids. This study proposes using surface modification of antibodies and viruses to increase their solubility in ionic liquids increasing protein thermal stability whilst retaining their protein biological function.