Rapid bioreactor process optimization and scale-up for production of a measles vector COVID-19 vaccine candidate

The emergence of SARS-CoV-2 in late 2019 and subsequent worldwide spread and pandemic in 2020 spurred the rapid and agile development of a variety of vaccine candidates. With speed to patients in mind during development of measles-vectored vaccine candidate V591, process optimization efforts were made to expand options for raw material sourcing/treatment, enable flexible use of various types of processing equipment, and streamline the overall production process. To that end, both gamma irradiated and heat sterilized microcarriers were tested to expand the supply network for critical process development experiments and manufacturing at a time when worldwide supply chains were strained or disrupted. Single use bioreactors were also evaluated and implemented to reduce experimental turnaround time. Furthermore, to simplify the process and gain additional efficiencies in large scale media preparation, growth and infection media formulations were harmonized with a parallel vaccine development program. These rapid process option evaluations were conducted parallel to critical path scale up, and the combined efforts enabled the rapid demonstration of two full manufacturing scale 2000 L bioreactors less than 6 months after virus seed delivery, culminating in the first large scale measles production process capable of addressing the high dose demands of a pandemic response scenario. Despite subsequent clinical discontinuation of the V591 vaccine candidate, the findings described herein will be useful for enabling rapid and scalable production of other measles-vectored vaccine candidates, oncolytic measles strains, or cell and gene therapies.