[Ip-health] US ramps up swine flu protection

[Sangeeta]

Published online 3 June 2009 | Nature | doi:10.1038/news.2009.543
Corrected online: 4 June 2009
News: Briefing
US ramps up swine flu protection
New technologies may help boost H1N1 vaccine production.

Declan Butler

More swine flu vaccine is needed
The United States has awarded a US$90-million contract to biotech company
MedImmune to produce a new live attenuated virus vaccine against influenza A
(H1N1) swine flu. The 1 June announcement follows the placing of almost $1
billion in vaccine-supply contracts to pharmaceutical companies a fortnight
ago.

Nature News analyses the likely impact of these efforts on domestic and
world ability to mobilize sufficient swine flu vaccine - and the importance
of deploying new technologies to boost production capacity.

Why the rash of announcements from the United States now?

The US government has cottoned on to the cruel mathematics: current flu
vaccine production capacities fall short of what would be needed in a
pandemic.

Rather than just awarding new vaccine-supply contracts, the government is
hoping to implement new technologies that could effectively boost the amount
of vaccine available from existing manufacturing capacity. These include
creating new live-virus attentuated vaccines and testing adjuvants that
boost the immune response of pandemic flu vaccines. Potentially some
vaccines may also be produced more quickly - perhaps providing enough to
protect first responders - by making them in caterpillar cells, rather than
in the usual hens' eggs.

How does the $90-million live attenuated vaccine contract help?

The virus in a live attenuated vaccine multiplies in vaccinated people
without causing illness. It can therefore be given in much lower doses than
a killed virus or an antigen subunit vaccine, effectively increasing vaccine
supply 30- to 100-fold (see Vaccine decisions loom for new flu strain).
MedImmune, based in Gaithersburg, Maryland, already makes a live attenuated
seasonal flu vaccine, FluMist, which is approved for use in the United
States for those aged 2-49 years old.

It's not yet clear that this contract will increase vaccine capacity much.
The efficacy of a new H1N1 vaccine will only be apparent once clinical
trials have been carried out. Also, MedImmune's own production capacity is
limited, and it will be hard for government to persuade other vaccine makers
to turn their egg vaccine plants over to live attenuated vaccine production.

If the other vaccine contracts are the traditional sort, how will they help
increase production capacity?

As part of the $1-billion contract, the US government has awarded Sanofi
Pasteur $191 million, Novartis $150 million, CSL Biotherapies $180 million
and GlaxoSmithKline (GSK) $38 million to supply H1N1 vaccine antigen. But
these companies will also be testing adjuvants, chemicals that boost the
capacity of the vaccine to stimulate an immune response, meaning that you
can stretch the available vaccine to cover more people. The United States
will be buying $283 million worth of adjuvant from Novartis and GSK to test
alongside vaccine antigen.

"Someone has gotten the message, someone is listening," says Robert Webster,
a flu virologist at St Jude Children's Research Hospital in Memphis,
Tennessee. Webster, who developed some of the first subunit antigen flu
vaccines, says these lost the "marvellous adjuvant effect of whole virus
vaccines; it's absolutely the case that we need these new adjuvants to give
that same effect."

Are there any other new technologies for increasing our vaccine stores?

One hope is to compress the production cycle: growing the virus in hens'
eggs takes time. Although the US Centers for Disease Control and Prevention
in Atlanta, Georgia, last week began shipping seed vaccine strains of the
novel swine H1N1 virus to vaccine manufacturers, substantial amounts will
not flow until October.

New technologies hold out the promise of producing flu vaccine in weeks, but
almost all are still in the research stage. One possible practical option is
a flu vaccine produced by Protein Sciences of Meriden, Connecticut, in
suspensions of cells of the caterpillar Spodoptera frugiperda that have been
infected with a baculovirus carrying genes for virus surface proteins. The
company could in principle start rolling out a swine flu vaccine within six
weeks, and was the only new vaccine technology company to be invited to a
World Health Organization (WHO) meeting in Geneva two weeks ago on swine flu
vaccine strategy.

Protein Sciences received word last week that it will receive a federal
contract to produce swine flu vaccine, and so will be able to purchase some
much-needed extra manufacturing capacity. At present, it can only produce up
to 30,000 doses a week. It has applied for an FDA licence for its 'FluBlok'
vaccine for adults in April 2008 and expects a decision by October, says
chief operating officer Manon Cox. The company hopes to get emergency
clearance for a swine flu vaccine and will run clinical trials this month on
its H1N1 vaccine candidate.

Globally, what are the latest figures on how much vaccine the world might be
able to produce, and when?

The figures vary depending on how much virus antigen is needed, whether one
or two doses are needed, and how successful any adjuvants are. The WHO's
initial estimates last month were that if current world production capacity
was all switched over to a H1N1 vaccine, the amount available by this
Christmas could range from just over a billion doses to less than 500
million.

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WHO's expert committee on vaccines has since said that up to 4.9 billion
doses could be available in 12 months, but real data will only be available
this summer. For the moment, the WHO's new higher estimates are 'wildly
optimistic', says David Fedson, a pandemic-vaccine expert and former
employee of Aventis Pasteur MSD, a joint venture European vaccine company
owned by Aventis Pasteur and Merck in the US.

How much vaccine are developing countries likely to get?

The picture here isn't bright. The WHO is trying to negotiate for 10% of
global production to be set aside for developing countries. If, for example,
860 million doses are available by Christmas, that would mean just 86
million doses; if two doses were needed per person, it will be only enough
for 43 million people. That's "a drop in the bucket," Fedson says. But if
there is aggressive political leadership to focus on maximizing output by
diverting production capacity to a mix of adjuvants, live attenuated virus
and maybe caterpillar-cell vaccines, there is just the possibility of having
more than enough vaccine to go round. That remains a remote hope.

Corrected:

The original version of this article incorrectly stated that MedImmune was
based in Cambridge, Massachusetts