Cell-based Flu Vaccine Candidate to Seek Approval

For the past 50 years, vaccine manufacturers in the United States have used egg-based technology to develop the seasonal influenza vaccine, and they might have stuck to this method were it not for the emergence of the H5N1 virus in Asia. Since its appearance in the mid-1990s, the highly pathogenic strain of influenza, which jumped directly from birds to humans, has resulted in 500 cases and 300 deaths.

Fortunately, the H5N1 virus, though among the deadliest strains identified thus far, has not spread efficiently, but the possibility of a global pandemic capable of killing more than 50% of its victims was enough to persuade public health authorities that the field needed major upgrades in both the design and manufacturing of pandemic and seasonal influenza vaccines.

At the Third Annual Influenza Congress USA conference in Arlington, Virginia, which opened today and runs through Thursday, researchers from both the US government and private industry said an influenza vaccine candidate made by Novartis Vaccines & Diagnostics that relies on faster cell-based technology and that eliminates the need to grow the influenza virus in fertilized chicken eggs will be seeking regulatory approval shortly from the US Food and Drug Administration for what would be the first cell-based candidate in the country that produces the most influenza vaccines.

David Hering, senior director of Key Accounts and US Government Contracts at Novartis, said the vaccine, which is currently available in Europe, could conceivably be on the market in time for the tail end of the 2012-2013 flu season. Cell-based manufacturing technology allows vaccine production to be initiated once a pandemic virus strain is identified without the need to adapt the virus strain to grow in eggs, as with traditional vaccine technologies.

The cell-based technology will shave several months off the vaccine manufacturing process. It now takes about nine months from soup to nuts to manufacture a seasonal flu vaccine, a timetable that proved to be problematic two years ago when the H1N1 pandemic surfaced and public health authorities were suddenly faced with having to produce a completely new influenza vaccine for a global population that had no pre-existing immunity to the strain.

Novartis’ work in cell-based technology reflects a public-private partnership (PPP) with the Biomedical Advanced  Research and Development Authority (BARDA), a branch of the US Health and Human Services Department. Along with Novartis, BARDA also has contracts with a number of other pharmaceutical companies, including GlaxoSmithKline Biologicals, Sanofi-Pasteur and MedImmune, to streamline influenza vaccine manufacturing process. The cell-based technology requires about six months to make a vaccine and is a viable alternative to strains of avian influenza that cannot be grown in eggs.

Robert Huebner, deputy director of BARDA’s Influenza Division, said the goal was to make the process more nimble so that at least 50 million trivalent doses of influenza vaccine or 150 million monovalent doses could be produced within four months after declaration of a pandemic. “We’re better prepared, but we’re still late getting influenza vaccine to the public,” says Huebner.

Together, Novartis and BARDA have spent about US$1 billion on the cell-based technology process, which includes a brand new state-of-the-art facility in North Carolina that is about to open and where the vaccine will be manufactured.

But the abbreviated schedule of cell-based technology, while a long time in coming, could soon give way to even faster methods that rely on recombinant DNA technology. A vaccine that now takes six months to develop may take a matter of weeks, noted Alan Shaw, chief scientific officer of VaxInnate, whose company has developed a seasonal influenza vaccine candidate, now in clinical trials, that uses efficient, low-cost recombinant protein methodologies in bacteria, namely E. coli. 

“Influenza used to be the sleepy backwater town of vaccine manufacturing,” said Shaw, noting the dozens of flu vaccine candidates in development right now. “It’s really remarkable what is happening.”