Rapid screening and scaled manufacture of immunogenic virus-like particles in the ALiCE cell-free protein synthesis system

The recent SARS-CoV-2 pandemic brought renewed attention to the susceptibility of mankind to new and re-emerging diseases, and highlighted the necessity for timely vaccine development to slow the spread of disease. Virus-Like Particles (VLPs) are a very promising alternative to traditional vaccine platforms as they trigger strong and lasting humoral and cellular immune responses in humans, with fewer safety concerns and higher stability than other platforms such as inactivated viruses and RNA vaccines. Here we present the use of ALiCE®, a commercially available tobacco-based cell-free protein synthesis system, to rapidly screen and produce highly immunogenic Hepatitis B-core virus-like particles. We show that VLP production was successfully scaled to 1L, resulting in a 20,000 fold scaling with no loss in yield, leading to the potential production of up to 100,000 vaccine doses.