The Development of a Cost-Effective and Stable Single Administration Vaccine Formulation to Achieve Vaccination Regiment Reduction

Abstract

Single administration technology is increasingly important for enhancing vaccination rates and reducing logistical burdens, particularly in resource-limited settings. Due to factors such as higher manufacturing costs and formulation challenges related to reduced antigen stability and low antigen loading or burst release, no Single Administration Vaccine (SAV) technology has reached the market yet. Various particle engineering methods and a range of carrier materials have been utilised in literature to encapsulate antigens and control their release. This work utilises PLGA, a regulatory-approved polymer found in marketed long-acting injectable formulations, to encapsulate a model antigen (BSA) through spray drying. Characterisation techniques such as XPS, HAXPES, and ToF-SIMS revealed that a high protein load beneath the surface layer of PLGA leads to burst release, which was not mitigated by increasing PLGA concentration. A novel formulation process utilising microfluidics as the critical step for PLGA microsphere generation was developed. This process improved encapsulation efficiency from 55% to over 97% and increased actual BSA loading from 20% to around 50%, while minimising burst release from 85% to less than 5%. Through a breadth of studies exploring different process parameters, including PLGA grades, surfactants, and buffers, the process was extensively optimised, effectively overcoming the common trade-off where higher loading usually results in increased losses to the outer aqueous phase. Notably, the developed process enabled a tunable pulsatile release profile while maintaining the stability of model antigens, thereby addressing the two major formulation challenges of SAV. Also, high antigen loading potentially reduces cost-related translational barriers by minimising the use of carrier materials in the finished dosage form. Meanwhile, the well-known scalability of the microfluidics process through parallelisation lowers expenses associated with resources and re-work of formulations upon scale-up, thereby streamlining manufacturing. Using the developed process, tetanus and flu antigens were encapsulated, achieving high loading and controlled release profiles. In the future, the technology is anticipated to be evaluated in preclinical animal models and further progressed into innovative SAV products for patient benefit.