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

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.