An intensified manufacturing process developed to support a trial of an Ebola vaccine in Uganda could help accelerate the production of other jabs in future health emergencies, according to Italian CDMO, ReiThera.
CEO, Stefano Colloca, told GEN: “The intensified process is aimed at increasing the productivity per unit of volume—volumetric productivity—by setting up culture conditions that allow the HEK-293-derived packaging cell line to grow at high density.
“This was achieved by including, in the fermentation process, a perfusion step carried out in a stirred tank bioreactor. This change resulted in a four-fold increase in production yield,” he said.
ReiThera modified the “packaging” HeK-293 cell line by inserting a transcriptional repressor that shuts down transgene expression. This increased productivity had a positive effect on the genetic stability of the vector, Colloca said.
In addition, the modified cell line was adapted to grow in suspension, which also helps make the process faster and easier to scale than traditional manufacturing methods, according to Colloca.
“The production process was designed to be scalable in a stirred tank bioreactor and therefore is based on a packaging cell line adapted to suspension followed by an extensive purification process combining depth filtration, ultrafiltration, and two steps of chromatography.
“In addition, we introduced a selective precipitation step for host cell DNA before proceeding with endonuclease digestion. This additional step allows us to get rid of host cell DNA very efficiently.”
He added, “The entire production process—both upstream and downstream—is mainly conducted using single-use technologies in order to facilitate accelerated changeover between production campaigns.”
Ebola vaccine
Using the process, ReiThera made 20,000 doses of vaccine for the Phase II study, which was initiated by Washington D.C. headquartered nonprofit organization, the Sabin Vaccine Institute (SBI), in Uganda earlier this year.
The vaccine—which is based on the ChAd3 simian adenoviral platform—achieved promising results in a Phase I clinical trial. In addition, 1,100 doses of the jab used as an emergency measure helped contain an Ebola outbreak that occurred in 2022, according to the SBI.
Colloca said, “Manufacturing took place at ReiThera’s facility located south of Rome, close to the international airport,” adding “we are preparing for the commercial production of the vaccine.”
ReiThera has plans to use the intensified production process more widely, according to Colloca, who says, “The strategy implemented by ReiThera for manufacturing and accelerated lot release can be used for other platform technologies in an emergency situation.”
