Vaccine Dreams

Each year, a new strain of seasonal influenza is born in Southeast Asia and sweeps across the globe to North America and Europe, infecting between 3 million and 4 million people annually before burning out somewhere in South America. World Health Organization (WHO) workers collect samples from flu sufferers in more than 80 countries to monitor current strains and to predict the strain that will become the year's killer. They are often wrong, however, and vaccine manufacturers can't simply whip up a new batch.

The lag time between identifying the breakout strain, manufacturing the vaccine, and distributing it to where it's needed can take six to nine months. With seasonal flu, those who fall ill may lose a few days of work, but H5N1 avian flu is poised to become the next pandemic, and there's no room for error. Last month, Konstantin Fiedler, who heads GE Healthcare's Growth Initiatives in Life Sciences, visited WHO headquarters in Geneva to tell them about an alternative: a recently announced collaboration between GE Healthcare and Maryland-based NovaVax to create a disposable vaccine factory for avian flu that can manufacture vaccine more quickly and at a much lower cost. The collaboration leverages GE's disposable bioreactors with NovaVax's virus-like particle (VLP) platform.

Ultrastructural details of an influenza virus particle.

Most vaccine manufacturers grow a genetically modified form of influenza in an egg or cell culture medium, and then process it to create either an inactivated virus vaccine or a live-attenuated vaccine in steel vats that need to be sterilized. They also add adjuvants to help stimulate the immune system so that smaller quantities of viral material are required. This is a labor-intensive process, however, and in the event of a major outbreak, manufacturers will be unable to meet a rapid surge in demand. Commissioning and building a vaccine plant can take as long as four years and cost close to $200 million. "For avian flu, you don't want to rely on bird eggs to breed new vaccines," says Fiedler.

Using just the genetic sequence of the virus, NovaVax bionengineers VLPs that are coated with the surface proteins of influenza, have the same structure as influenza, but are unable to replicate and, therefore, present no threat of infection. Because antigens are presented in their native three-dimensional conformation, they are highly immunogenic without requiring costly adjuvants. A similar technique is currently used in Merck's vaccine against human papillomavirus, but NovaVax is the only company that has succeeded in getting the technique to work for influenza. The companies claim that, with the plastic bioreactors, they can manufacture these particles in just 12 weeks after learning the sequence of the dominant strain.

Rahul Singhvi, president and CEO of NovaVax, says that the collaboration began unofficially in late 2005 when a member of the sales team at GE Healthcare offered to supply custom tubing fixtures to link equipment that NovaVax was using in vaccine manufacturing - equipment from the then-independent Wave Biotech and GE Healthcare. After that project came to a close, researchers from NovaVax and GE had a dinner meeting, where Singhvi outlined the plan to create a disposable vaccine factory. "The idea resonated with them," says Singhvi.

The disposable factory can be set up in half the time and at a quarter of the cost of the steel vats used in traditional factories. "One of the dreams," says Fiedler, "is to put a vaccine factory on a truck, put that truck in Africa, and position those trucks in several places when there is an epidemic developing." That $200 million facility would cost only $40 million, according to the companies. On top of that, the portable facility can be refurbished and reused to produce other vaccines beyond the present pandemic.

NovaVax's VLPs are in Phase II clinical trials, and NovaVax has already constructed a prototype $5 million factory at its Rockville location. Fiedler and Singhvi say they could have their product on the market in two to three years, something that would not be possible without GE's manufacturing equipment and its international footprint. "[Customers] obviously know about GE," Singhvi says, "but they may not know about NovaVax."