The economics of virus-like particle and capsomere vaccines

• Microbial synthesis of virus-like particle (VLP) and capsomere (CAP) vaccines simulated with SuperPro.
• Economical production of VLP and CAP vaccines under 1 cent per dose of vaccine.
• Rapid production of VLP and CAP vaccines, 320 million doses in timespan of days.
• CAP cost 69% lower than VLP due to simpler process and higher yield.
• Process risk analysis performed with Monte Carlo stochastic simulation.

Effective control of infectious diseases relies on new vaccine technologies that can quicken and broaden vaccine delivery. Novel modular virus-like particle (VLP) and capsomere technologies have been recently reported. These technologies utilize murine polyomavirus (MuPyV) VLPs and capsomeres as potent delivery systems to carry and display antigenic modules consisting of heterologous peptides, in the form of modular constructs capable of inducing high levels of specific antibodies against bacterial or viral antigens. These constructs are prepared using high-yield microbial synthesis, potentially enabling low-cost, rapid and scalable manufacture of new vaccines. To evaluate this potential, this study analyzes the economics of capsomere and VLP production using process simulation. Data here show that the unit production cost (UPC) for capsomere is up to 69% lower than that for VLP at the comparison scale (500 L fermentor), due to a simpler downstream process and a higher product yield. For VLP production, reactive diafiltration assembly was shown to have a UPC 30% lower than dilution assembly. Sensitivity analysis of uncertain process inputs with Monte Carlo simulations revealed a significant influence of final biomass concentration on UPC, contributing up to 50% of variance observed in the UPC probability distribution. Despite such process variability, optimized capsomere or VLP vaccine production, using a 500-L or 1500-L fermentor respectively, has more than 80% chance of producing vaccine at a cost less than 1 cent per dose based on a conservative assumption of 50 μg protein per vaccine dose. With a 10-kL fermentor, both the capsomere and VLP processes have productivity that could allow manufacture of 320 million vaccine doses in 2.3 and 4.7 days, respectively. This study confirms with quantitative data the possible economic, speed and scale benefits of the modular capsomere and VLP vaccine technologies, which can potentially redefine current vaccine distribution landscape and time-scale benchmarks.