Cutting-Edge Technique Helps Produce Pandemic Flu Vaccine

Influenza, or the flu, is a respiratory infection caused by the flu virus. In Canada, flu season usually runs from November to April and an estimated 10-25% of Canadians may get the flu each year.

Flu vaccines have been around since the 1940s. The vaccine is made up of inactivated flu viruses that have been grown in fertilized hens' eggs and then purified. The flu viruses are capable of changing from year to year, so the composition of the vaccine has to be updated annually. This is why it is necessary to be immunized each fall.

After you get a flu shot, your immune system produces antibodies against the strains of virus in the vaccine. The antibodies are effective for four to six months. When you are exposed to the flu virus, the antibodies help prevent infection or reduce the severity of the illness.

H5 & H7 Viruses and the Flu Pandemic

The severity of the flu season depends on two things: the susceptibility of the population and the type of flu virus.

Occasionally, certain strains of flu viruses cause worldwide epidemics, or pandemics, with high rates of illness or death. Historic evidence suggests that pandemics occurred three to four times per century. In the last century there were three flu pandemics: "Spanish flu" in 1918-1919, "Asian flu" in 1957-58, and "Hong Kong flu" in 1968-69.

It is believed that the kind of flu viruses most likely to cause a pandemic in the future will arise through genetic mixing between human and avian influenza viruses. Pigs, which can be infected with both human and avian influenza viruses, may act as vehicles for this genetic mixing.

Two of the avian influenza viruses of greatest concern are H5 and H7. Both are highly pathogenic, meaning that they have the ability to cause significant disease very quickly.

The Limitation of Traditional Vaccine Production

Since the 1970s, flu vaccines have been grown in fertilized hens' eggs. Although this process creates an effective and safe flu vaccine against most viruses, it is too time-consuming and too dependent on a steady supply of eggs to be reliable in the face of a pandemic emergency.

But there is another limitation with the traditional method of producing flu vaccine: H5 and H7 are so pathogenic they cannot be successfully grown in hens' eggs as they quickly kill them. H5 and H7 are rapidly lethal to embryonic hens' eggs.

So how can we respond most quickly and effectively to a future pandemic, given the fact that the virus will likely be a strain of H5 or H7?

Using Reverse Genetics to Produce a Pandemic Flu Vaccine

Recently, a strain of H7 called H7N3 was found circulating in British Columbia. Two people working in close contact with the infected B.C. poultry have had mild infections, and since recovered.

Dr. Yan Li, Head of Respiratory Viruses at Health Canada, is leading a team to develop a vaccine for H7N3 using a special technique called "reverse genetics." This cutting-edge work will help the international community respond more quickly and effectively to a future pandemic that most likely will result from a virus similar to H7.

According to Dr. Li, "The research we're doing is important for developing the most rapid method to provide a vaccine "seed" virus that is not presently available. The reverse genetics strategy is particularly useful when a virus is especially pathogenic, as is the case with H7N3."

The reverse genetics technique that is being used by Dr. Li to develop a vaccine against H7N3 is a complicated procedure, but can be summarized as follows:

• The team isolates the H7N3 virus from the patients.
• Two genes called HA and NA are selected from the H7N3 virus. These genes are essential for producing a vaccine - they code for the special proteins that help our bodies to produce the proper antibodies, or resistance, to the H7N3 virus.
• Sections of these HA and NA genes are then specially "clipped" so that the virus coded by the genes is no longer pathogenic - and, no longer deadly to chicken eggs.
• The HA and NA genes from H7N3 are then combined with genes from another virus strain called PR8 which is very good at reproducing quickly and is proven safe to humans.
• The resulting genetic combination (genes from H7N3 + genes from PR8) produces proteins that make up virus particles that make our bodies resistant to H7N3 but can be reproduced in chicken eggs. These virus particles then reproduce very quickly in the eggs to produce a safe and effective vaccine against H7N3.

At present, Dr. Li and his team have "disarmed" the HA genes and are currently confirming that its pathogenicity is successfully reduced. Once both the HA and NA genes are successfully "disarmed" and combined with the PR8 genes, this "recombined" virus particle will be replicated to create a vaccine. The vaccine will then be tested for effectiveness on animals.

According to Dr. Li, "While the technology to generate this kind of virus particle is available and readily implemented, there are still a number of challenges to producing a vaccine for a future pandemic.

"For example, it's unlikely we would have enough embryonated eggs available for emergency use. Rather, we need to identify and approve alternative kinds of cells for large-scale vaccine production. Also, we don't have the capacity to manufacture vaccines on a large scale, so we will need to partner with a company that has the capacity for large-scale vaccine production."