Principle of CF-1 and CF-2
Production of
an immunogenic trivalent poliovirus virus-like particle vaccine candidate in
yeast using controlled fermentation
Abstract
The success of the poliovirus (PV) vaccines
has enabled the near-eradication of wild PV, however, their continued use
post-eradication poses concerns, due to the potential for virus escape during
vaccine manufacture. Recombinant virus-like particles (VLPs) that lack the
viral genome remove this risk. Here, we demonstrate the production of PV VLPs
for all three serotypes by controlled fermentation using Pichia pastoris. We
determined the cryo-EM structure of a new PV2 mutant, termed SC5a, in
comparison to PV2-SC6b VLPs described previously and investigated the
immunogenicity of PV2- SC5a VLPs. Finally, a trivalent immunogenicity trial
using bioreactor-derived VLPs of all three serotypes in the presence of
Alhydrogel adjuvant, showed that these VLPs outperform the current IPV vaccine
in the standard vaccine potency assay, offering the potential for dose-sparing.
Overall, these results provide further evidence that yeast-produced VLPs have
the potential to be a next-generation polio vaccine in a post-eradication
world.
Not only has the CF-1 allowed us to move
our science forward from a technical point-of-view, it was also a necessity
from a scientific viewpoint. Our poliovirus VLPs are temperature sensitive,
consequently if these VLPs are exposed to temperatures above 40°C, they undergo a conformational
shift, increasing the size of the particles. This increase leads to these
particles no longer being able to induce a long-term protective immunological
response. Therefore, the CF-1’s ability to cool samples during the cell
disruption process meant that we were able to maintain the correct conformation
of our VLPs, allowing us to test these VLPs in animal models. The success of
these trials has led to these VLPs being transferred to industry for Phase I
clinical trials.
About The
Continuous Flow Cell Disruptor
Both models benefit from a HMI control, a
maximum process pressure of 40kpsi (2700 bar), integrated sample cooling
jacket, 200mL inlet reservoir (hopper), auto shut down feature for when the
process is complete and both models take advantage of Constant Systems precise
and consistent hydraulic control which is fully scaleable through the whole
product range from 0.5mL single preparation processing to large volume
processing at 150L per hour. This precise control ensures that the entire
sample is processed at the operators set pressure to ensure accurate and
consistent results and in most cases a single process or pass is adequate
meaning multiple passes are not required. Both models are capable of processing
fluid or re-suspended sample types and are utilised for many sample types such
as bacteria, yeast and algae.
CF1 Model At
approximately 700mm² the CF1 is small enough to bench mount if required but is
best suited when used on its tailor made trolley. The CF1 trolley ensures that
the equipment is situated at its optimum working height and is mounted on full
swivel and lockable casters that enables safe and free movement of the
equipment when needed. The CF1 is recommended for process volumes in the range
of 15mL through to 10L. For those processing larger volumes in this range then
the CF1 can be offered with an integrated peristaltic pump fully controlled
through the HMI which will ensure that the inlet reservoir is continually fed
whilst recirculating the sample to help avoid any settling until the entire
sample is processed.
CF2 Model With
a footprint of approx. 700mm² the CF2 is a floor standing model that is
recommended for process volumes from 15mL through to 100L. The CF2 is offered
with an integrated peristaltic pump as standard. The CF2 is mounted on full
swivel and lockable castors that enables safe and free movement of the
equipment when needed.
If you have any further questions, please don't hesitate to contact us.
SUNWAY official website : https://www.sun-way.com.tw/
Tel : 02-27718337
Fax : 02-27414646
SUNWAY official E-mail address : mrkt@sun-way.com.tw