Siena

Boosting demand could help vaccine manufacturers keep their facilities open. Credit: Novartis AG

Influenza experts are recommending an extensive vaccination programme against seasonal flu in developing countries, in part to boost demand for vaccines so that firms can ramp up production to cope with pandemics. The message came from scientists and policy-makers who met on 2–3 July in Siena, Italy, to assess the gaps in their knowledge about the current H1N1 pandemic virus.

The governments of many developing countries remain to be convinced that flu is a major danger for their citizens relative to other health problems, says Abdullah Brooks of the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh. Yet Brooks presented research showing that around one-third of pneumonia deaths in children younger than 2 years old in his region can be attributed to the influenza virus. According to the United Nations agency UNICEF, pneumonia kills more than 2 million children under the age of five each year — more than any other disease.

At the meeting, experts recommended that pilot studies be conducted in developing countries to measure the prevalence of flu virus in sick children, and to assess how much a flu-vaccination programme would reduce the burden of disease in the countries. UNICEF, health charities and the governments of rich nations would probably be approached for financial support.

As well as providing a major public-health benefit, the effort could create a larger, more stable market for seasonal flu vaccines in the future. "A few months ago we were discussing whether we would need to close some of our manufacturing plants because we were losing so much money on flu vaccines," says Rino Rappuoli, head of vaccine research at Novartis in Siena, adding that the current H1N1 pandemic has helped to avert any closures as governments race to stock up on vaccines. For example, the firm was awarded US$289 million by the US Department of Health and Human Services (HHS) in Bethesda, Maryland, in May to produce H1N1 vaccine antigen as well as an adjuvant to amplify the immune response to the vaccine, thus reducing the amount of antigen needed in each shot and stretching manufacturing-plant capacity. Other vaccine companies, including GlaxoSmithKline, Sanofi Pasteur, CSL Biotherapies and MedImmune, will also benefit from $643 million in HHS orders.

The US Food and Drug Administration (FDA) has yet to approve any flu vaccines that contain an adjuvant, a cautious response to the possibility that adjuvants could trigger autoimmune disease on very rare occasions. Yet in 2000, the European Medicines Agency approved Novartis's seasonal flu vaccine Fluad, which contains MF59 — an adjuvant based on squalene, a complex hydrocarbon that is the biochemical precursor to steroids. Novartis says that it has sold 45 million vaccination shots containing MF59, and that no side effects have been reported other than occasional inflammation at the injection site. "It isn't really clear what additional safety data the FDA could be waiting for," says Peter Palese, a virologist at Mount Sinai School of Medicine in New York. And a study published earlier this year has shown that MF59 can broaden the effectiveness of an H5N1 vaccine to tackle several similar viral strains — an effect that could potentially be applied in H1N1 vaccines as well (G. Galli et al. Proc. Natl Acad. Sci. USA 106, 7962–7967; 2009).

The consensus of the meeting was that H1N1 vaccines, which could be given to billions of people this year, should contain an adjuvant. These vaccination programmes will provide a unique opportunity to identify any extremely rare side effects, says virologist Albert Osterhaus of the University of Rotterdam, the Netherlands, as long as they have "mechanisms to monitor all cases of autoimmune disease to see if the vaccine is really to blame."