March 25, 2005
Caterpillar Cells May Accelerate Flu Vaccine Production

Caterpillar cells and genetically engineered bacilovirus might provide a better means to make influenza vaccines.

BALTIMORE, MD -- March 21, 2005 -- Using a strategy involving a genetically modified baculovirus and caterpillar cells scientists from Protein Sciences Corporation have been able to speed up a key step in the development of an experimental cell-based influenza vaccine. They report their findings today at the 2005 American Society for Microbiology Biodefense Research Meeting.

"The bird flu may become the next flu pandemic strain. It could happen at any time," says Keyang Wang, a scientist at Protein Sciences Corp. and a researcher on the study. "The most effective method to control such an outbreak is the widespread use of a vaccine. The traditional egg-based method requires 3 to 6 months to develop the vaccine. With our cell-based method, the time from receipt of the virus strain to the final vaccine product would be shortened to approximately 1 to 2 months."

Wang is absolutely correct to state that the current chicked egg-based method for manufacturing vaccine takes a long time. Plus, it can not easily be scaled up quickly. Should a big killer influenza strain break out into human populations existing vaccine manufacturers would be hard pressed to produce billions of doses of influenza vaccine. My guess is they would be able to satisfy only a small fraction of the demand for vaccine.

The existing approach for making vaccines in eggs might not work with a killer avian influenza strain. The egg embryos might be killed by the virus before much vaccine could be produced.

Today's flu vaccines are prepared in fertilized chicken eggs. The eggshell is punctured, and the influenza virus is injected into the fluid surrounding the embryo. The egg is then resealed, the embryo becomes infected, and the resulting virus is then harvested, purified and used to produce the vaccine. In addition to the long development time, another drawback to this method is the possibility that an avian influenza virus would be lethal to embryos in the eggs.

The vaccine strategy pursued by Protein Sciences, known commercially as FluBlok, does not rely on whole vaccine virus. It uses a purified concentration of a key molecule on the surface of the virus, called hemagglutinin, to elicit an immune response against that specific strain of the virus.

Wang and his colleagues have developed a methodology for rapidly producing and purifying hemagglutinin from an influenza virus. They extract the genes responsible for the production of hemagglutinin from the virus and insert them into a baculovirus. Caterpillar cells are then infected with the virus and begin to produce the hemagglutinin.

The FluBlok vaccine has recently finished phase II clinical trials, where it has established safety and the ability to elicit a strong antibody response in humans.

"Since all the media used here are chemically stable and commercially available, the process can be easily scaled up for commercial manufacture," says Wang. "New FluBlok vaccines can be developed quickly and safely to address late appearing influenza viruses and to reduce the impact of a potential flu pandemic."

It is interesting to note that this vaccine is being developed by a commercial company. The US government and other governments have been slow to respond to the need for vaccines that can be manufactured more rapidly and for which manufacturing can more easily be scaled up. Both capabilities are needed in order to produce large numbers of vaccine doses should a major killer influenza strain become established in human populations. With that thought in mind it is worth looking at more of what Protein Sciences has to say for itself.

The FluBlØk™ vaccine may even provide more protection than current commercially available vaccines.

FluBlØk™, derived from Recombinant hemagglutinin (rHA) is a patented replacement vaccine for the current licensed vaccines that are produced in eggs using 40-year old technology. FluBlØk™ consists of three rHA proteins corresponding to the flu strains selected by the World Health Organization and the Center for Disease Control for each year's vaccine. These proteins are produced in serum free insect cells and formulated in PBS without preservatives or adjuvants. Clinical trials have shown safety and efficacy in healthy adults and the elderly population:

  • Several Phase I and II trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID) involving over 600 subjects demonstrated safety and efficacy as reported in four published studies in the Journal of Infectious Diseases. A significantly higher percentage of elderly subjects receiving a higher dose of our vaccine develop protective antibody titers compared to the licensed vaccine.

If this vaccine lives up to its claims it will both work better and be faster and easier to manufacture.

This vaccine is made using a virus to infect caterpillar cells grown in culture.

There are many advantages of using the baculovirus expression system, including: high expression levels, limitless size of the expressed protein, efficient cleavage of signal peptides and processing of the protein, post-translational modifications and simultaneous expression of multiple genes. In addition to these advantages, expressed proteins are correctly folded and biologically active. Human clinical studies have demonstrated that proteins produced in the baculovirus expression system can be safely administered to humans. Because the cells die during the manufacturing process, the BEVS system is uniquely able to produce proteins from genes of unknown function.

If you page down to the bottom of that list link you'll see a graphical chart comparing how this vaccine production method compares to several other vaccine production methods in terms of speed, cost, glycosylation (coating of virus antigen proteins with sugars that would be found on them naturally), folding (vaccine proteins have folded 3 dimensional shapes that need to be duplicated), and ease of FDA approval.

I wish these folks luck in their attempts to bring their vaccine to market. We'd all be better off with an influenza vaccine that can be made more rapidly and cheaply and which even elicit a stronger immune response. This vaccine may even save many of our lives some day.

Share |      Randall Parker, 2005 March 25 04:30 PM  Dangers Natural Bio

Patrick said at March 28, 2005 6:35 PM:

Even if we never have another flu pandemic, a cheaper, more effective and faster vaccine will still save thousands of lives a year.

Shows who the real heros in our society are.

Jim said at March 30, 2005 9:05 AM:


that is a great development, if it works out. a friend who used to be involved in the drug development business from the business side of things explained to me how terrible a business the flu-vaccine business is. it's practically charity. nobody wants to pay much to get a shot to prevent a disease they probably won't get and would most likely survive with only a few days of downtime. while the production is a time-consuming process that must be planned well in advance. if mistakes are made during processing all the blame gets put on this company, but if they are very successful, nobody appreciates the epedemic avoided.

i'm impressed that it's a private company - innovative start-ups are the fuel of our economy!

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