Dose-sparing strategies for pandemic influenza

Drug giants Novartis and GlaxoSmithKline (GSK) have been awarded contracts with the US government to develop adjuvant technology for pandemic influenza, to potentially increase the number of doses to be distributed among US citizens.

Recent figures imply that pandemic flu vaccine production, even at peak capacity, will only make vaccines available to 10 per cent of the US population. This has prompted the US Department of Health and Human services (DHHS) to call on proposals on ways to 'stretch the domestic influenza vaccine supply in the event of an influenza pandemic.'

The DHHS has invested $118.3 million into research on adjuvant technology - a substance added to a vaccine to improve the body's immune response - used in combination with a vaccine's active constituent, the antigen, which has potential to lower the amount of antigen used per dose of H5N1 influenza vaccine.

A third contract, worth $128 million, has been awarded to Iomai to develop an immune-boosting skin patch that, when used in combination with an injectable influenza vaccine, requires 10- to 100-times less vaccine.

Recent clinical data has shown that H5N1 pandemic vaccines require two doses to stimulate an immune response in humans and that up to 90 micrograms of antigen is used per dose, in comparison to seasonal influenza that uses 15 micrograms of antigens in a single dose.

Both Novartis and GSK have addressed this problem with their proprietary adjuvant technologies, as an example Novartis' MF59 has been included in several studies where it was found that it might reduce the amount of antigen needed for an immune response. In addition, MF59 can potentially provide cross-protection against changing flu strains.

Around two-thirds of GSK's vaccines in development are formulated with their proprietary adjuvant technology. In 2005, GSK boosted its presence in the vaccines field with the acquisition of its long-term US vaccines partner Corixa, which produced adjuvants contained in many of their vaccines. However, the pandemic flu adjuvant, details of which will not be disclosed until 3 March 2007, will be developed in a plant in Belgium, according to Graeme Hacking, GSK spokesperson.

"Novartis is committed to the development and supply of vaccines to help protect against both seasonal influenza as well as the possible emergence of pandemic influenza," said Jörg Reinhardt, CEO of Novartis Vaccines and Diagnostics.

"The use of our proprietary adjuvant MF59 with influenza vaccines has shown to be dose sparing and to provide additional immunogenicity against a broader range of potential pandemic influenza strains, while using lower amounts of viral antigen for the vaccine."

"A limited global supply capacity of flu antigen makes it critical that we use innovative adjuvant system technology to produce a new generation of flu pandemic vaccines," said David Stout, president of pharmaceuticals at GSK.

In 2006, DHHS made a bulk order of $40m (€31m) of bulk H5N1 antigen - representing 800,000 doses - to GSK, that will build on the existing US stockpile of about 5.9m doses of H5N1 vaccine. GSK was also awarded $274m to develop cell-culture technology to speed the development of new cell-culture-based seasonal and pandemic influenza vaccines, and to scale-up cell culture manufacturing capability at its Pennsylvania site.

In addition, DHHS announced it had also awarded contracts to two other drugmakers - Sanofi-Pasteur and Novartis - to supply flu vaccines. The three drug firms will make enough doses to cover 2.7m people for $200m worth of vaccines against the H5N1 avian flu virus, DHHS said.

"Having a stockpile of influenza vaccine that may offer protection against the H5N1 virus is an important part of our pandemic influenza preparedness plan," said HHS secretary Michael Leavitt.