Tuesday, July 1, 2014

MaxCyte's New Technology Could Help Vaccine Shortages



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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