Anthony Doesburg: For some, flu scare is turning sunny side up

If there are winners from the swine flu pandemic, poultry farmers are likely to be among them. As pharmaceutical companies gear up to produce a flu vaccine, millions of hen eggs are being used to grow the cells from which the vaccine is made.

Egg suppliers to CSL Biotherapies, the Melbourne-based company that is the nearest vaccine manufacturer to New Zealand, are having their business boosted by about 300,000 eggs a day as production of the influenza A (H1N1) vaccine is ramped up. Each egg yields roughly one dose of vaccine.

"We have three suppliers with four farms," says CSL spokeswoman Rachel David, who supply "biological standard" eggs. "We have an integrated supply chain so we work very closely with them to ensure our standards are met."

CSL's production method involves taking a flu strain, or "isolate", supplied by the World Health Organisation (WHO) or the US Centres for Disease Control and Prevention, and injecting it into fertilised eggs. The embryo becomes infected and the virus multiplies. It is then harvested, purified and made inactive before the vaccine is formulated. Although much of the process is automated, the initial stages are labour-intensive.

"Our plant and equipment are state of the art in terms of automation," David says. "However, there are several steps that have a manual component, particularly at the beginning of the process where we need to alter the virus to ensure that it is safe to work with and that it grows well."

A new technique involves not working directly with the virus, but synthesising it in the lab from its genetic code, sequenced and supplied as a computer file by the WHO. "We did that but, as it turned out, the live isolate worked better."

A number of pharmaceutical companies, including US-based Baxter, which began full-scale swine flu vaccine production a fortnight ago, grow the virus in cells - typically mammalian kidney cells - rather than eggs. One benefit of cell-based vaccines is that they can be given to people allergic to eggs.

Cell-based production has another advantage, says Lance Jennings, a Canterbury District Health Board virologist and key figure in developing New Zealand's pandemic response plan. "The cell culture process can use the original virus strain whereas the egg-manufacturing process uses reassorted viruses."

"Reassortment", which means combining the wild H1N1 flu strain with a strain known to grow well in eggs, is an added step in the production process. Six weeks to two months after receiving the isolate, full-scale production can begin.

"Amplifying the virus in eggs or by the cell culture process, which uses big vats of cells, then produces large volumes of virus suspension that needs to be purified," Jennings says.

Cell-based vaccine production uses the whole virus, whereas egg-based manufacturing has an additional purification step to remove egg protein.

"The rate delimiting step is then moving that bulk viral suspension - the vaccine - into syringes or vials, labelling, packaging and then distributing."

The swine flu pandemic will result in an upturn in business for ferret farmers, too. CSL conducts clinical trials first with ferrets, then humans, to ensure the vaccine does what it's supposed to do.

"Some ferret studies have been completed," David says, "and clinical trials in human volunteers will commence in mid-July."

Principally, the human trial is designed to find the appropriate vaccine dose, which is determined by blood tests.

"The initial trial will involve 240 healthy adult volunteers who will receive two injections of the vaccine, three weeks apart, and will compare a standard with an increased dosage of vaccine." A separate study will be carried out with children.

What happens with the vaccine from there is unclear. For a number of reasons, it's not a foregone conclusion that governments would immediately start vaccinating their populations.

For one thing, as Jennings puts it, the "burden of disease" associated with the virus doesn't appear to be as severe as it could have been. But there is some fear that, as with the 1918 flu pandemic that killed millions worldwide, it could return in a more virulent form.

If that happens - and Jennings says there was evidence from Brazil last week that the virus is evolving - the record from 1918 suggests exposure to the milder form may provide protection from the nastier version.

Also comforting is that the vaccine developed against the 2006 bird flu (H5N1) outbreak appears to offer cross-protection from subsequent H5N1 strains, suggesting a swine flu vaccine administered now might stave off later strains.

One thing is for sure. Poultry and ferret farmers won't be the only ones to make a swine flu killing. CSL's David says the Australian Government has ordered 10 million doses of vaccine and the US wants US$180 million ($287 million) worth.

Counting doses

How many doses of H1N1 vaccine can manufacturers churn out? World Health Organisation estimates range from at least one to two billion doses a year, up to a maximum of 4.9 billion doses a year. Those numbers don't automatically translate to the number of people who can be vaccinated, says the WHO, as it isn't known how many doses will be needed for protection.

Anthony Doesburg is an Auckland technology journalist.