9 May 2007

I. Development of pandemic influenza vaccine

What is the difference between seasonal influenza vaccines, "pre-pandemic" vaccines, and pandemic vaccines?

• Seasonal influenza vaccines refer to vaccines that are updated yearly and that protect against currently circulating influenza viruses. What is sometimes referred to as "pre-pandemic vaccines", contain antigens that correspond to H5N1 influenza strains, as these are thought to be most likely to cause a pandemic.
• Pandemic vaccine is a vaccine of the future with unknown antigenic composition. It will protect against the pandemic influenza strain but will only be available after the emerging virus of the next influenza pandemic has been isolated. Persons vaccinated may need a booster dose to be fully protected.

Where do we stand in terms of developing an effective pandemic influenza vaccine?
Several experimental vaccines have been shown by industry to induce the type of immune response in human volunteers which is thought to be protective. This being said, a definitive demonstration of efficacy can only be obtained when these vaccines are tested in a pandemic. One H5N1 influenza vaccine has been licensed by the United States Food and Drug Administration and a number of the most advanced candidate vaccines against H5N1 avian influenza might be registered within six months to two years. Pending the actual type of the real pandemic virus, these vaccines might be found protective against the virus causing the next pandemic.

What are the most promising avenues for short and medium term development of pandemic influenza vaccine? What are the most promising research projects to date?
Several streams of development are promising: among them, inactivated split (the technology currently used for seasonal influenza vaccines) vaccines with an adjuvant, whole virus vaccines and live attenuated vaccines. Other approaches are more upstream in the development pipeline.

How close are we to developing the ideal pandemic influenza vaccine?
An ideal influenza vaccine that would protect against all strains of influenza is still very much upstream in the pipeline, and might not be available in the next five to 10 years.

Will a vaccine be a magic bullet to control an influenza pandemic?
The importance of pandemic vaccine is its reduction of health consequences during a pandemic. There is no magic bullet to control an influenza pandemic. A comprehensive approach to pandemic control includes a combination of non-pharmaceutical interventions, use of antiviral drugs and vaccines; this is the best way to mitigate the impact of an influenza pandemic.
In addition, effectively responding to a pandemic goes beyond responding to disease alone. Effective communications, monitoring of the impact of the pandemic, identifying unusual clinical disease manifestations, for example, are part of effective pandemic planning.

How long will it take to produce the first doses of pandemic influenza vaccine in the event of a pandemic?
If production of a vaccine starts on the day a pandemic is declared, it is thought that at least four to six months will be necessary to produce the first doses of vaccine.

II. The WHO Global pandemic influenza action plan to increase vaccine supply (GAP)

What are the chief obstacles to ensure universal access to pandemic influenza vaccine?
One of the chief obstacles is that global vaccine production capacity is insufficient, mainly because the market demand for seasonal influenza vaccine is limited. In many countries, influenza remains a little recognized problem or the cost of influenza vaccine is too high and therefore the demand for influenza vaccine is low. In addition, many competing health problems in developing countries require urgent attention and financial investment.

Is industry building more capacity to produce influenza vaccine?
Industry is already moving towards increasing vaccine production capacity substantially, based on expected increase of the market demand for seasonal vaccine. It is expected that current capacity could nearly double by 2009.

What is the expected lifespan of the GAP activities? What exactly are the first results that could be seen in three to five years?
Activities need to be sustained over at least five to 10 years. In three to five years:

• We will have an accurate idea of the current global situation in terms of production capacity.
• We will have a better idea of how to maximize the number of potentially available doses of vaccine from current production capacity.
• We will see the results of efforts to move towards newer technologies such as those using cell-based production and other novel techniques.
• We will see movement towards increased vaccine production capacity in both industrialized and developing countries with a combined vaccine production capacity potentially above 3 billion doses per year.

What are the most important activities that you would fund first?

• Conduct a thorough survey of current and medium term vaccine production capacity, and of anticipated demand.
• Conduct a comprehensive research project to try and improve current low production yields with inactivated vaccines made from H5N1 vaccine strains.
• Establish new capacity for influenza vaccine production in developing countries.
• Investigate a variety of dose-sparing approaches that would permit the immunization of more people.

How do you expect to obtain the necessary funding: US $3-10 billion? Have you gotten pledges ? If so, from whom and for how much?
Obviously, no single donor can provide such a level of funding. The amounts mentioned do include projected investments by the private sector, and it is expected that countries, and in particular wealthy countries, invest into activities prioritized in the GAP. In addition, foundations could play a major contributing role. The US government has pledged US$ 10 million towards establishing new capacity for influenza vaccine production in developing countries. Japan has contributed US$ 20 million to UNICEF and WHO for vaccine preparedness activities, and Canada is pledging CDN$ 1 million.

If a pandemic occurs and there is a severe shortage of pandemic influenza vaccine, what scenarios can we imagine? You predict this could lead to a public health crisis — what would that be like?
In this situation, the importance of non-vaccine related control measures would assume even greater importance. These include:

• Effective communications to provide accurate information and reduce unnecessary anxiety;
• Consideration of early implementation of potential population-based interventions, such as travel advisories and social distancing; and
• Efforts to stretch the available supplies of antiviral drugs as much as possible.

Should countries pre-purchase pandemic influenza vaccine?
At present, WHO has not made any recommendations to countries about the pre- pandemic purchase of potential pandemic vaccine, but consultations are ongoing to identify the most appropriate strategies. Moreover, pre-purchase of vaccine is a national decision.

Does WHO recommend vaccination as soon as we get a safe, effective vaccine against the currently circulating avian influenza virus?
There are two fundamentally different ways in which a vaccine against H5N1 could be possibly used:

• First, to protect selected populations at risk of getting infected by viruses currently circulating among poultry. For example, potentially, a vaccine could be used to protect farming populations or families with backyard flocks in affected countries.
• The second use would be to pre-immunize large general populations or selected groups (e.g. health workers) against a potential pandemic. Many of the vaccines being developed may prove to be both safe and capable of stimulating development of immune protection against some H5N1 viruses.

WHO´s expert groups point out that the pandemic virus may be quite different than what people are immunized against and therefore the vaccine may not be protective, and that any decision about whether to use avian flu vaccines as a hedge against pandemic influenza must be done so with full knowledge of this fundamental uncertainty. In the best scenario, such use of a vaccine would prove life saving. In the worst, it would only have little effectiveness, and some experts consider such a use of the vaccine as an unfounded expenditure. WHO continues to review all of the scientific, health and social benefits and drawbacks with its experts and policies are regularly updated.

How important is vaccination (compared to other control activities such as use of antivirals, social distancing and infection control) to stemming a flu pandemic? (especially given the lag time to actually produce the appropriate vaccine)
All of these actions are complementary and none replaces another action. Nonetheless, for individuals, only vaccines (beside natural infection) can provide pandemic strain specific, prolonged individual protection. In contrast to antiviral drugs, vaccination is required only once or twice for one or two years if the pandemic strain does not undergo too much antigenic change, while antiviral drugs must be taken daily. If a pandemic vaccine can be made available in large quantities in a timely manner, it will have a central role in protecting people against pandemic flu. If it is not available, then the other actions must be relied upon to protect people.

How will we ensure that low-resource countries get vaccine?
For the short term, WHO is working with UNICEF and industrialized countries to begin the process of mobilizing financial resources for purchase of vaccine for developing countries.
For the medium and longer term, two steps are critical:

• Documenting the impact of influenza in these countries and developing sustainable programmes of seasonal influenza vaccination, if appropriate in the national context
• Establishing influenza vaccine production capacity in developing countries to increase global production capacity and ensure equitable distribution of pandemic vaccine.