scientists hope of conquering flu pandemic

[Guest guest]

from The Times January 4, 2008

New vaccinations give scientists hope of conquering flu pandemic

Influenza virus protein spikes

Nigel Hawkes, Health Editor

A vaccine that could help to control a flu pandemic has shown

encouraging results in its first human trials.

The vaccine, made by Acambis, based in Cambridge, should protect

against all strains of influenza A, the type responsible for

pandemics. Unlike existing vaccines it does not have to be

reformulated each year to match the prevalent strains of flu, so it

could be stockpiled and used as soon as a pandemic strain emerges. Nor

does it need to be grown on fertilised chicken eggs, as the existing

vaccines do, but can be produced by cell culture.

The results, announced yesterday by Acambis, show that in human

volunteers the Acam-Flu-A vaccine was safe and produced an immune

response against its target, a small protein (peptide) called M2e that

is found on the surface of all A-strains of the flu virus. The vaccine

was also tested on ferrets, which are commonly used in flu research

because they are susceptible to human and bird flu.

The ferrets were divided into two groups and either vaccinated with

the new vaccine or left unvaccinated. They were then exposed to a

large dose of the H5N1 bird flu that has killed millions of chickens

and more than 200 people across Asia since 2003. All the unvaccinated

ferrets died, but 70 per cent of the vaccinated ones survived.

A significant problem with conventional vaccines is that they attack

parts of the flu virus that can change rapidly. Each season the World

Health Organisation identifies the three strains that are circulating,

normally two A-strains and one B, and the vaccine is made to order to

provide protection against them. It is always a race against time,

because millions of eggs have to be produced to grow the vaccine and

if it is not used it is out of date by the following season.

Acambis's approach was to identify some aspect of the virus that is

unchanging. Pandemics are invariably caused by A-strains of flu;

B-strains, which are found only in humans, may cause epidemics but

have never caused pandemics.

The company identified a peptide, M2e, on the surface of all A-strains

and developed a vaccine that targeted it. When an individual is

vaccinated the vaccine teaches the immune system to recognise and be

alert to the peptide so that as soon as flu arrives the body's

protective systems swing into action against it. To improve the

vaccine's effectiveness, it was combined in the trial with adjuvants,

chemicals that ginger up the immune system and improve its ability to

learn. The adjuvant called QS-21, made by Antigenics, proved to be the

best. When this was added, 90 per cent of those vaccinated had

antibodies against the M2e peptide.

, the executive vice-president for research and

development at Acambis, said: " If there was an immediate threat of

pandemic flu, it would be possible to complete the trials and market

the vaccine within three years. Without such a threat, it will likely

take longer, perhaps five years.

" The beauty of the vaccine is its simplicity. It could be used in

several different ways. First, we could produce a pre-pandemic vaccine

that we know would be effective against A-strains. If a bird flu

strain such as H5N1 turned into a pandemic strain we could get the

vaccine out of storage and use it. Alternatively we could use it as

soon as we got the slightest inkling of a pandemic strain emerging. Or

it could be used instead of the normal vaccine for protecting against

seasonal flu, with a vaccine against B-strains added. That would

depend on how effective it was, which we will only know after further

trials. "

The fate of millions

— Flu viruses can drift and shift. Drift refers to the continual small

changes that dictate the annual reformulation of the flu vaccine to

ensure that it works. Shift happens rarely and unpredictably, and

produces pandemics

— There were three shifts in the 20th century, causing pandemics in

1918, 1957 and 1968. Some virologists fear that another is overdue

— Pandemic strains strike human beings unprepared, and spread fast.

The 1918 pandemic killed 20 million, some say 40 million

— Shifts occur when avian strains infect human beings, or avian and

human strains share genes, as may be happening in Asia

— Since the H5N1 avian strain first appeared in 2003, a few hundred

cases have been transmitted to humans. About half of those have died,

but this is not yet a pandemic strain, and may never become one

http://www.timesonline.co.uk/tol/life_and_style/health/article3128119.ece