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Potential breakthrough for potential outbreaks

By Katrina Megget, 05-Jun-2007

Related topics: Processing & QC, Lab equipment & consumables , Processing (automation, control, separation)

One week - that would be all the time needed to produce a new vaccine against an infectious disease outbreak, according to initial data from a novel vaccine manufacturing technique.

Gone would be the cumbersome egg-based production techniques and developing cell cultures; the way of the future could be vaccines produced using the polymerase chain reaction (PCR).

US-based Vical's RapidResponse DNA vaccine platform, which has initially demonstrated a 100 per cent protection in mice against a lethal H3N2 influenza strain, appeared to tick all the right boxes - production of large quantities of vaccine in a matter of days, at a fraction of the cost.

"At this time, it is a real potential breakthrough," Vical executive director of investor relations Alan Engbring told US-PharmaTechnologist.com.

Using a cell-free process and chemical synthesis of the vaccine, the production could overcome the shortfalls of conventional vaccine manufacturing for diseases such as influenza, which uses killed or disabled viruses grown in chicken eggs or via cell culture, which take months to produce.

Engbring said using a PCR process would mean a vaccine could take just three hours to make after the initial pathogenic DNA had been sequenced.

In all, a vaccine could be produced within a week, meaning the technology could be crucial in addressing potentially pandemic diseases such as influenza or severe acute respiratory syndrome (SARS), or bioterrorist-modified pathogens such as anthrax or smallpox, as well as previously unknown pathogens.

"We are very excited about what we have found so far but there's a lot of scale up and testing that needs to be done," Engbring said.

Details of the vaccine production process were not disclosed, but essentially the process would involve the PCR of a piece of DNA that encodes part of a pathogen in question, creating a linear expression cassette (LEC).

PCR technology takes a segment of nucleic acid (DNA or RNA) and copies or "amplifies" it so that the nucleic acid can be more readily analyzed. Such technology is used in applications as in the detection of hereditary diseases, the identification of genetic fingerprints, the diagnosis of infectious diseases and the cloning of genes to exponentially amplify DNA via enzymatic replication.

The larger the PCR reactors the more product can be produced.

Currently, plasmid DNA vaccines, which involve a closed loop of DNA and are under development at Vical for pandemic influenza and other infectious diseases, are manufactured by bacterial fermentation in standardized equipment with a production time measured in weeks rather than months.

While plasmid DNA vaccines offered a significant improvement over conventional vaccine manufacturing technologies, Vical believed the RapidResponse DNA vaccine platform could offer further advantages.

Vical president and chief executive Vijay Samant said: "We remain excited by the potential of our plasmid DNA vaccines, and we will continue development of these programs because the technology is much closer to commercial realization in humans. But for eventual deployment against future emerging diseases, the RapidResponse DNA vaccine platform appears to offer significant potential advantages over plasmid DNA vaccines, and vast improvements compared with other current vaccine approaches."

The next steps in the development of the RapidResponse DNA vaccine platform would include determination of the lowest effective dose, head-to-head comparison against plasmid DNA vaccine, and scale-up in adherence with current Good Manufacturing Practices (cGMP) to production of quantities appropriate for initial human clinical trials.

The initial research was supported by a grant from the US Defense Advanced Research Projects Agency (DARPA).

Earlier this year Swiss drug major Novartis received a "positive opinion" from the Committee for Medicinal Products for Human use (CHMP) for its cell culture-derived seasonal flu vaccine OptaFlu.

Made in a mammalian cell culture, the approach would slash the time it takes to produce the antigens used in vaccines from months to weeks

Other advantages of cell-based production is that it is independent of the availability of eggs, and the vaccines produced do not run the risk of being contaminated with egg proteins, which can cause allergic reactions in some people.

Novartis is also concentrating on developing an H5N1 vaccine based on the cell culture technique.

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