H5N1 avian influenza – first steps towards development of a human vaccine

12 August 2005

On 6 August, government scientists at the US National Institute of Allergy and Infectious Diseases announced results from initial clinical trials of a vaccine being developed to protect humans against infection with H5N1 avian influenza. Preliminary data indicate that the experimental vaccine evoked an immune response in a small group of healthy adults.

Although more trials are needed, the new findings reconfirm the feasibility of developing an H5N1-specific vaccine.

H5N1 is presently considered the most likely virus to ignite the next pandemic. The increasing spread and evolution of H5N1 viruses in Asia have brought the world closer to another pandemic than at any time since 1968, when the last of the previous century’s three pandemics began.

Vaccines are the principal medical intervention for protecting individuals against pandemic influenza. If available rapidly and in sufficient quantities, they can reduce the morbidity and mortality that have traditionally made pandemics such socially disruptive as well as deadly events.

However, many problems need to be resolved before vaccines can assume such a role in mitigating the effects of the next pandemic. The most important need is to find vaccine formulations that make the best use of limited antigen supplies.

Antigen is the component of the vaccine that elicits an immune response. The US trial provides important insight into possible vaccine formulations. It used doses that are higher than the amount of virus antigen contained in influenza vaccines produced yearly for normal seasonal epidemics.

Strategies for stretching limited antigen supplies – by adding an adjuvant to the vaccine formulation or injecting the vaccine into the skin rather than into muscle – have been proposed. Adjuvants are chemicals that can be added to the vaccine formulation to boost the immune response, theoretically allowing the use of smaller doses of antigen to achieve an immune response. Such antigen-sparing strategies using adjuvants are currently being tested by several manufacturers, and preliminary results are expected within the next three months.

At present, 90% of production capacity for all influenza vaccines is concentrated in Europe and North America in countries that account for only 10% of the world’s population. Current global manufacturing capacity (estimated at 300 million doses of regular trivalent influenza vaccine per year) is inadequate to meet the expected global needs during a pandemic and cannot be rapidly augmented.

Influenza pandemics are unique infectious disease events that can spread to every country in the world within months, resulting in a high and universal demand for preventive and treatment measures. Pandemics thus throw into sharp relief inequities in global access to vaccines and other medical interventions during an emergency. Based on past experience, countries with local manufacturing capacity are likely to meet domestic demand for vaccines and other critical resources fully before freeing supplies for the export market.

Because the present total global manufacturing capacity for influenza vaccine is limited, any decision to manufacture a pandemic vaccine in large quantities prior to the start of a pandemic would, of necessity, compromise the capacity to produce vaccines for seasonal influenza. Seasonal epidemics of influenza predictably cause an estimated 250,000 to 500,000 deaths each year. In the current situation, the capacity to respond to seasonal influenza must be balanced against preparations for pandemic influenza. However, once a pandemic has been declared, all manufacturers would stop production of seasonal vaccines and produce only the pandemic vaccine.

WHO has produced advice on a broad range of preparedness measures that can be undertaken by countries, taking into consideration that adequate supplies of vaccine will not be available at the start of a pandemic in any country.

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