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Mar 1, 2009 (Vol. 29, No. 5)

DNA Vaccines Inch Toward Human Use

West Nile Virus Equine Product Gains Foothold for a Burgeoning Field

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    VGXI is developing a more effective way to manufacture a high-concentration multicomponent DNA vaccine.

    A DNA vaccine targeting West Nile virus in equines was launched in December by the Fort Dodge Animal Health division of Wyeth. That vaccine was reportedly the first DNA vaccine for any species to be registered with a government regulatory body. It was also one of the many milestones and advancements in DNA vaccine development and manufacturing methods outlined by speakers at the recent International Society of DNA Vaccines conference in Las Vegas, organized by BioConferences International.

    Wyeth’s development program proved that DNA vaccines can be as efficacious as traditional vaccines. “This was proof of concept for DNA vaccines as a class,” explained Hsien-Jue Chu, DVM, Ph.D., executive vp, animal health research and development. This is the fourth vaccine for West Nile virus to reach the market since Wyeth’s West Nile Innovator, launched in 2001, and two subsequent recombinant-based vaccines.

    In the early part of this decade, experimental DNA vaccines seemed effective in rodents, where “it was easy to induce an immune response. It was difficult to make it work in large animals, however,” Dr. Chu recounted. Success came when an immune-modulator was added to the plasmid DNA, which probably allowed the intramuscularly-injected DNA to target the cells more effectively. Now, the DNA-based West Nile vaccine confers at least one year immunity—the same duration of immunity that is demonstrated by traditional vaccines, he said.

    The lessons learned from the West Nile DNA vaccine program are being applied to rabies and other vaccines, he said, and work is under way to see whether it is possible to lengthen the conferred immunity. Programs at other companies, Dr. Chu said, involve DNA vaccines to treat melanoma in dogs and to target a particular pathogen in fish that affects salmon farms.

    Even before Wyeth launched its equine DNA vaccine targeting West Nile virus, companies were working to create the technologies needed to produce and scale-up aspects of DNA vaccine development.

  • Multicomponent Manufacturing

    VGXI is developing a more effective way to manufacture a high concentration multicomponent DNA vaccine. The benefit, according to Robert J. Juba, senior director of manufacturing and technical services, is that combination DNA therapies elicit elevated immune responses to multiple viral components or disease indications.

    VGXI’s manufacturing approach is based upon fermentation methods that generate high plasmid yield, purity, and  concentration. The company uses a 500  liter fermentation reactor that generates an average of 50 kilograms of paste and yields 50 grams of plasmid per cycle. A high- throughput recovery system relies upon continuous flow from lysis to capture, recovering 50 grams of plasmid in eight hours, Juba said.

    The lysis step uses high-shear, low residence cell lysis in combination with the VGXI Airmix® column to neutralize and separate the solution. “It’s very gentle,” Juba insisted. Multistage in-line filtration separates genomic DNA and cell debris for high plasmid purity. “No hold times are required,” he stressed.

    The company uses ion exchange and hydrophobic interaction membrane chromatography for plasmid enrichment and to remove undesired plasmid forms and residual endotoxin. Most importantly, it maximizes supercoiled forms of the plasmid and minimizes plasmid shearing. Plasmid concentration is achieved by recirculating the solution, after buffer exchange, through tangential flow filtration membranes, and sterile-filtered to achieve concentrations of up to 15 mg per mL.

    This manufacturing process has been used successfully for a smallpox vaccine that contained eight different plasmid components that was developed by VGXI. The company is also developing multi-component DNA vaccines using this technology for HPV and influenza.


Readers' Comments

Posted 05/15/2009 by Engineer

This is a very interesting article.

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