Developing globally accessible thermo-stable vaccine adjuvants using flexible and adaptive manufacturing processes.

疫苗挽救了数百万人的生命。它们是预防传染病的最有效、最具成本效益的方法。疫苗接种导致全球消灭天花，实际上消灭了脊髓灰质炎，白喉、破伤风、百日咳、麻疹、腮腺炎和风疹的发病率降低了95%以上。疫苗接种还大大降低了疾病发病率，这对于良性但经济上重要的感染尤其重要：估计60%的医生转诊和住院治疗是由200多种病毒引起的呼吸道感染引起的。尽管疫苗取得了进展，但全球获得可预防疾病疫苗的机会仍然面临明显障碍：据估计，全世界仍有1 940万婴儿无法获得基本疫苗。为了在全球范围内提供疫苗，需要从生产商到接受者不间断地供应高质量疫苗。目前，这一供应链受到一系列因素的阻碍，包括疫苗供应不足，当地储存、处理和管理疫苗的能力有限，因为许多疫苗需要冷藏。因此，需要供应链的灵活性与耐热疫苗系统的开发相结合。广泛的研究表明，脂质体（小双层纳米颗粒）作为疫苗抗原的合适佐剂。它们的两亲特性和双相性质允许脂质体掺入抗原并提供保护和改善的递送。事实上，该项目的合作团队的工作已经证明，我们可以控制脂质体的物理化学属性（包括大小，电荷和双层刚性和组成），以提高佐剂的功效。因此，通过利用脂质体，我们能够减少生产有效疫苗所需的抗原量，从而提高疫苗产量。因此，我们可以使用这些纳米颗粒在疫苗生产中提供经济效率，并降低其生产成本和时间。除了它们的佐剂性质外，申请人还证明了通过将抗原掺入这些双层纳米颗粒中，可以稳定蛋白质抗原。因此，脂质体有可能避免对疫苗冷链供应的需要，并提高当地的能力和供应。因此，脂质体佐剂的应用提供了增强疫苗生产和增强分布的机会。然而，目前的脂质体生产方法目前是费力和耗时的。本项目旨在开发热稳定的脂质体佐剂，其可以使用灵活和自适应的工艺制造，可以以快速响应的模式按比例放大和缩小。为了实现这一目标，我们将1）研究脂质体制剂在控制疫苗效力中的作用，2）通过利用脂质体的稳定特性形成热稳定的疫苗系统，3）开发创新的微流体工艺，以一步连续加工方法生产这些掺入抗原的脂质体佐剂。该项目得到了史泰登血清研究所（SSI）的支持。该项目的候选人拥有硕士学位，并受到SSI和她的学术导师的强烈推荐。SSI将通过提供一系列生物制剂和体内研究提供实物财政支持（7.5万英镑），SSI将为候选人提供3至6个月的安置。

Vaccines have saved millions of lives. They are the most powerful, most cost-effective, way to prevent infectious diseases. Vaccination has led to the global eradication of Smallpox, the virtual eradication of Polio, and a reduction of over 95 % in the incidence of diphtheria, tetanus, pertussis, measles, mumps and rubella. Vaccination also greatly reduces disease morbidity, which is particularly important for benign yet economically important infections: an estimated 60 % of medical doctor referrals and hospitalization result from respiratory tract infections, caused by over 200 viruses. Despite advances in vaccines, global access to vaccines for preventable diseases continues to face notable barriers: it is estimated that 19.4 million infants worldwide are still missing out on basic vaccines. To provide global access to vaccines, an uninterrupted supply of high-quality vaccines, from manufacturer to recipient is needed. Currently this supply chain is hindered by a range of factors including insufficient vaccine supply and limited local capacity to store, handle and administer vaccines as many require refrigeration. Therefore agility in the supply chain combined with the development of a thermostable vaccine system is required. A wide range of studies have shown liposomes (small bilayer nanoparticles) act as suitable adjuvants for vaccine antigens. Their amphiphilic character and biphasic nature allow liposomes to incorporate antigens and provide protection and improved delivery. Indeed work from the collaborative team for this project has demonstrated we can control liposomal physicochemical attributes (including size, charge and bilayer rigidity and composition) to enhance adjuvant efficacy. Therefore, by exploiting liposomes we are able to reduce the amount of antigen required to produce effective vaccines and hence enhance vaccine yield. Thus we can use these nanoparticles to deliver economically efficiencies in vaccine manufacture and drive down their cost and time of manufacture.In addition to their adjuvant properties, the applicants have also demonstrated that by incorporating antigen within these bilayer nanoparticles protein antigens can be stabilised. Thus, liposomes could offer the potential to circumvent the need for cold-chain supply of vaccines and improve local capacity and supply. Thus, the application of liposomal adjuvants provides opportunities in enhancing vaccine production and enhanced distribution. However, current liposome production methods are currently laborious and time-consuming. The present project aims to develop thermostable liposomal adjuvants which can be manufactured using flexible and adaptive processes, which can be scaled up and down in a rapidly responsive mode. To achieve this, we will 1) investigate the role of liposome formulation in controlling vaccine efficacy, 2) format a thermostable vaccine system by exploiting the stabilising properties of liposomes and 3) develop innovative microfluidic processes to produce these liposomal adjuvants incorporating antigen in a one-step continuous processing method. This project is supported by the Staten Serum Institute (SSI). The candidate for this project has a Masters and is highly recommended both by SSI and her academic supervisors. SSI will provide in-kind financial support (£75k) through provision of a range of biologicals and in vivo studies and SSI will host the candidate for a 3 to 6 month placement.