[health-vn] Vaccine makers are ill-prepared for an influenza pandemic

[Vern Weitzel]

http://www.economist.com/science/displayStory.cfm?story_id=13611194&source=features_box_main

Preparing for the worst
May 7th 2009 | NEW YORK

 From Economist.com

Vaccine makers are ill-prepared for an influenza pandemic

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MEXICO CITY sprang back to life this week after two weeks of fear and 
inactivity. Officials shut down most of the economy to halt the spread of a 
previously unknown strain of the mongrel H1N1 virus, which is comprised of 
avian, swine and human influenza viruses. The hope is that the outbreak has now 
peaked.

If so, that will come as a relief to many, as the virus has spread rapidly 
around the world. On Wednesday May 6th the World Health Organisation (WHO) 
reported 822 confirmed cases in Mexico, including 29 deaths. Altogether, 403 
cases have been detected in the United States, including at least one death. 
Dozens of non-lethal cases have been found in 22 other countries. If a cluster 
of self-sustaining cases in a region outside the Americas is confirmed, the WHO 
will raise its concern from level five to the top of its six-level scale for 
global pandemics.

Richard Besser, the acting director of America’s Centres for Disease Control 
(CDC), said the virus “so far is not looking more severe than a strain that we 
would see in seasonal flu.” That is not as reassuring as it sounds. An influenza 
outbreak in 1918 began in a mild way, but returned in a lethal form months later 
and killed millions. Margaret Chan, the WHO’s boss, cautioned: “it may come 
back…the world should prepare for it.”


One of the best ways to do so is vaccination. Surveillance systems and antiviral 
treatments will help contain a disease, but they cannot halt it the way a 
vaccine could. Such a treatment would have to come from the makers of vaccines 
for the more ordinary, seasonal strains of flu. Yet despite all the advances in 
biological science, this industry still relies on capital-intensive, inflexible 
and old-fashioned technologies, such as producing vaccines from millions of 
chicken eggs.

The production of flu vaccine has developed to cope with seasonal flu. The 
disease may seem no more than a nuisance to many, but the flu still kills 
perhaps 500,000 people a year around the world. It is hard to develop a perfect 
vaccine against seasonal influenza because it is so fleet-footed. There are 
usually several different strains of influenza active at any time, and these 
variations evolve. Alan Barrett of the University of Texas says travel by 
carriers of influenza, be they people in aeroplanes or birds on the wing, means 
regional mutations quickly spread around the world. Hence, even when flu 
subsides at the end of the northern hemisphere’s winter, the disease merely 
shifts to the southern hemisphere (which is now entering its winter). Six months 
later, it moves back. When the mutations are gradual, as with seasonal flu, it 
is known as drift; when they are abrupt, as with the new strain of H1N1, you 
have a shift on your hands.

To help the vaccine manufacturers plan, the WHO issues guidelines every six 
months listing the three strains of seasonal flu that appear to pose the biggest 
threat during the relevant hemisphere’s approaching winter. The firms then 
prepare their genetic cocktails and develop them inside live chicken eggs in 
sterile conditions. The resulting “trivalent” vaccine provokes the patient’s 
immune system into producing antibodies, and that primes it for an attack by the 
worrying strains of flu.

The final product comes in two forms. Most of the world’s flu vaccine is a 
killed virus, given as an injection; Europe’s Sanofi Pasteur and Novartis are 
leading producers that use this approach. America’s MedImmune has come up with a 
nasal spray that uses a live flu virus in a weakened form. Both methods use lots 
of eggs.

If a global pandemic is declared and manufacturers are asked to produce a 
vaccine for H1N1, they are unlikely to be able to respond quickly enough. Firms 
can produce perhaps a billion doses of seasonal vaccine every year. The details 
of dosing for a pandemic vaccine are not yet known, but it is clear that even if 
all the capacity was switched to pandemic flu there would still be a huge global 
shortfall. Keiji Fukuda of the WHO summed it up this way: “There’s much greater 
vaccine capacity than there was a few years ago, but there is not enough vaccine 
capacity to instantly make vaccines for the entire world’s population for 
influenza.”

Switching production also poses risks. A lack of vaccines for seasonal flu 
guarantees that many unprotected people will die of the otherwise mundane 
version of influenza. Nor is there any guarantee that, having switched 
production, a second wave of an H1N1 strain will indeed be deadly. So producing 
pandemic vaccines as a precaution may turn out to be a waste of resources with 
deadly results. Or it may save millions of lives. No one knows.

The main problem is that egg-based manufacturing cannot mount a rapid response. 
It could take only a few more weeks for the WHO and CDC to develop a “seed” 
strain of the pandemic virus, but experts say producers would then need four to 
six months before they could create large volumes of vaccine.

Could more innovative manufacturing techniques help? One promising approach 
involves growing vaccines not in eggs but in cell cultures, which is speedy and 
easily scaled up. Another is to add adjuvants, which are catalysts that improve 
the efficacy of a vaccine and reduce the amount of active ingredient required.

A number of companies have been hoping to get such technologies to the market by 
2011 or 2012, and some might be able to help with any shortfall should there be 
a pandemic later this year. Anthony Fauci, head of America’s National Institute 
of Allergy and Infectious Diseases, says the American government has been 
funding many such firms in preparation for bioterrorism and pandemics. But he 
points out that none of the firms has so far got a pandemic flu vaccine past 
safety trials. “They are not ready for prime-time,” he says.

Yet desperate times may lead to desperate measures. Cell-based manufacturing is 
already used to make vaccines against many other diseases, so it might win rapid 
approval for flu. European regulators have been more enthusiastic than American 
ones about allowing adjuvants in flu vaccines. Mexican officials are reportedly 
in discussions with biotech firms to build flexible vaccine-facilities quickly. 
The WHO this week called such novel approaches a risky “leap of faith”. But if a 
crisis does engulf the world, that may be a leap some are willing to make.