Mice Protected From Hepatitis C Virus Using New Vaccine Technology

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Mice Protected From Hepatitis C Virus Using New Vaccine

Technology

25 Feb 2011

Three percent of the world's population is currently

infected by hepatitis C. The virus hides in the liver and

can cause cirrhosis and liver cancer, and it's the most

frequent cause of liver transplants in Denmark. Since the

virus mutates strongly, we have no traditional vaccine, but

researchers at the University of Copenhagen are now the

first to succeed in developing a vaccine, which provides

future hope for medical protection from this type of

hepatitis.

"The hepatitis C virus (HCV) has the same infection pathways

as HIV," says Jan Pravsgaard Christensen, Associate

Professor of Infection Immunology at the Faculty of Health

Sciences, University of Copenhagen.

"Approximately one newly infected patient in five has an

immune system capable of defeating an acute HCV infection in

the first six months. But most cases do not present any

symptoms at all and the virus becomes a chronic infection of

the liver."

Poorly treated donor blood and dirty needles are sinners

Every year three or four million more people become infected

and the most frequent path of infection is needle sharing

among drug addicts or tattoo artists with poor hygiene, such

as tribal tattoo artists in Africa and Asia. Fifteen percent

of new infections are sexually transmitted, while ten

percent come from unscreened blood transfusions.

According to Allan Randrup Thomsen, Professor of

Experimental Virology, "Egypt is one country with a high

incidence of HCV. This is particularly due to lack of

caution in the past with regards to screening donated blood

for the presence of this virus," he says.

China, Brazil, South East Asia and African states south of

the Sahara also have a high incidence, while the disease is

also spreading through Eastern Europe, especially Romania

and Moldova.

HCV mutates too fast for traditional vaccines

The new vaccine technology was developed by J. Holst,

a former PhD student now a postdoc with the Experimental

Virology group, which also includes Professor Allan Randrup

Thomsen and Associate Professor Jan Pravsgaard Christensen.

The technology works by stimulating and accelerating the

immune system, and showing the body's defence mechanisms of

the parts of the virus that are more conserved and do not

mutate as fast and as often, such as the molecules on the

surface of the HCV.

Basically, traditional vaccines work by showing the immune

defences an identikit image of the virus for which

protection is desired. Antibodies then patrol all entrances

with a copy of this image and are able to respond rapidly if

the virus attempts to penetrate. But the influenza virus

mutates its surface molecules and in the course of a single

season it takes on a new guise so that it no longer

resembles the original identikit image and the vaccine loses

its efficacy.

Professor Randrup explains, "Mutations of the surface are

Darwin at work, so to speak. The virus tries to outwit the

immune defences and if it succeeds we get ill, and our

response is new vaccines."

Associate Professor Pravsgaard Christensen says, "Viruses

like HCV mutate so rapidly that classical vaccine technology

hasn't a chance of keeping up. But the molecules inside the

virus do not mutate that rapidly, because the survival of

the virus does not depend on it."

New vaccine technology gives immune system information

about virus' stable parts

According to Professor Randrup, the body's natural defences

usually don't see these internal virus molecules until the

virus has taken residence in the body.

"Our cells constantly show random samples of their contents

to the immune defence patrols, and if there are enough

foreign bodies among them, the alarm is triggered," says

Professor Randrup.

The cells display fragments of the surface molecules and

internal genes from the virus, and if you show the immune

defences a kind of X-ray of the inner genes, they will

respond. Actually, the response is extremely potent, and one

of the things it does is summon the specialised CD8 killer

cells.

"We took a dead common cold virus, an adenovirus that is

completely harmless and which many of us have met in

childhood," Associate Professor Pravsgaard Christensen

explains.

"We hid the gene for one of the HCV's internal molecules

inside it. At the same time we attached a special molecule

on the internal molecule so that when the cells of the mouse

body tried to take a sample, they would extract a more

extensive section. The immune defences would then be

presented with a larger section of the molecule concerned.

You may say that the immune defences were given an entire

palm print of the internal genes instead of just a single

fingerprint."

This strategy resulted in two discoveries from the team.

Firstly, the mice were vaccinated for HCV in a way that

meant that protection was independent of variations in the

surface molecules of the virus. Secondly, the immune

defences of the mice saw such an extensive section of the

internal molecule that even though some aspects of it

changed, there were still a couple of impressions the immune

defences could recognise and respond to.

The new technology to be tested in monkeys

Another virus that mutates its surface molecules with

extreme rapidity is HIV. It changes skin in the space of 24

hours, and like HCV, we do not yet have a cure or a vaccine.

The researchers think that HIV originally migrated to man

from monkeys in the 1930s, when it was the simian

Immunodeficiency virus that still circulates among a number

of species of wild African monkeys.

"The Danish Medical Research Council (DMRC) has given

postdoc Holst a grant to test our technology for a SIV

vaccine for macaque monkeys in the US," says Associate

Professor Pravsgaard Christensen.

The University of Copenhagen is also currently negotiating

the sale of the patent for the process so that the

technology can be developed for use in human vaccines.

The discovery of an effective HCV vaccine has just been

published in the Journal of Immunology.

Source:

Associate Professor Jan Pravsgaard Christensen

University of Copenhagen

Article URL:

http://www.medicalnewstoday.com/articles/217431.php

Main News Category: Liver Disease / Hepatitis

Also Appears In: Immune System / Vaccines, Blood

/ Hematology,

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Bill Eastman

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