The outbreak
of the H1N1 virus in 2009 and the resulting vaccine shortage demonstrated the
costly and often lengthy process associated with vaccine production. While stable cell lines have been the
standard in biotherapeutic protein production for the last 20 years,
researchers have been anxious for more efficient technology. Transient transfection technology, including MaxCyte’s
Flow
Electroporation, largely meet some of these efficiency
demands. MaxCyte recently published a whitepaper
looking at how this meets some of the demands in vaccine production. You can download the article
here, but you may want to
see what Dr. Weili Wang, one of the lead scientists on this study, had to say on the implications.
The report says that
no other single expression system has the capability to produce the series of
next-gen vaccines. What are the implications of this on the field?
MaxCyte
electroporation is a clinically proven transient transfection method that
enables early risk reduction and accelerated development of antibodies,
recombinant antigens, VLPs, VRPs, viral vectors, and cell immunotherapies. In
addition, it enables the progression from gene to gram-scale quantities of
proteins within days rather than weeks. This means, in the field vaccines for
pandemics, seasonal outbreaks, or biodefense needs could be generated much
quicker than it currently is.
What can this
contribute to the field of cell line engineering?
With more than a
dozen adherent and suspension cells lines currently in use by vaccine
manufacturers, a transfection platform that provides cell type flexibility is
clearly needed. MaxCyte electroporation consistently results in high levels of
transfection efficiency and cell viability for a wide range of cells, including
CHO, MDCK, BHK-21, Vero, NS0, insect cells, and other cell types commonly used
for protein expression. Furthermore, cell immunotherapy using patient-isolated
primary cells, most frequently hematopoietic cells, requires high transfection
efficiency and low cell toxicity while meeting stringent sterility and safety needs.
MaxCyte electroporation was originally developed for this application, which is
why it has extremely high levels of cell viability and transfection
efficiencies for a range of primary cells. Together the ability to transfect a
wide range of cells, including difficult-to-transfect cells, and the high
transfection efficiencies and cell viabilities could greatly expand the field
of cellular immunotherapy.
Looking at this data,
what jumps out at you the most as something you didn’t expect?
The data reinforce our previous experiences with the wide
range of cell types it can transfect, including insect cells. Insect cells are
commonly used in vaccine production since they post translationally modify
proteins in a manner similar to that of mammalian cells and are easy to culture
with simplified cell growth that is readily adapted to high-density suspension.
While both transient transfection and recombinant baculovirus platforms are
commonly used for insect cell protein expression, MaxCyte electroporation
offers a more rapid means of production since there is no need to make
baculovirus and it provides a higher yield because there is no need to remove
the baculovirus, which the literature has cited a reason for yield loss.
Let your imagination
run wild for a second, what’s the next innovation we could expect from this
type of technology?
The use of therapeutic
antibodies and vaccines is a large and growing area of interest. Over the next
several years we can expect to see more therapeutic products come to market,
particularly concerning rheumatoid
arthritis, multiple sclerosis, Alzheimer's disease, and different types of
cancers. This next generation of therapeutic products will be better at
targeting cancerous cells as exemplified by the exponential growth in
Antibody-Drug Conjugates (ADCs) and they will have dual targeting properties,
as exemplified by the growing body of research in bi- and multi-specific
antibodies, immunotherapies, and VLP vaccines. Flow electroporation will
be an integral part of the growing reliance therapeutic antibodies, since it
provides the best transfection efficiency and cell viability and accelerates
the process of biotherapeutic development by providing higher titers of protein
and significant savings in time, cost, and resources.
If you had one
sentence to express the implications of this paper, how would you explain it?
It is possible that
we will never face a vaccine shortage like we did in 2009-2010 with the H1N1
flu outbreak.
To explain, large-scale
cell culture-based vaccine has many advantages over egg-based production. It
provides a reduction in lead time, greater reliability, and greater
flexibility. The egg-based method requires 5-6 months for the production of enough
eggs and then another 9-10 months for the production of the final vaccine. With
the cell-based method, the 5-6 months needed to establish the egg supply is
eliminated as well as a portion of the 9-10 months since there would be no need
to adapt the virus to grow in eggs. Using the cell-based method also provides a
more reliable source for vaccine production. While eggs are perishable, cell
lines can be established and cryopreserved. Furthermore, there is growing
concern over the increase in avian influenza (H5N1). This is real threat to the
supply of chickens and embryonic egg used in vaccine production. A cell-based
method for vaccine production truly means we may never face a shortage again.
What’s one
implication from the findings that might be obvious to most people?
No one wants to be
faced with a vaccine shortage. We need to be able to quickly produce vaccines
at the quantity needed. MaxCyte electroporation is an important step in that
direction. With its ability to quickly scale-up to the necessary quantities
much faster than using stable cell lines.
Access exclusive speaker interviews from leaders in cell line development. Download the Cell Line Engineering & Development conference brochure here to check them out.
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