New Vaccine Technology Protects Mice from Hepatitis C Virus

[Guest guest]

http://www.sciencedaily.com/releases/2011/02/110223122258.htm

New Vaccine Technology Protects Mice from Hepatitis C Virus

ScienceDaily (Feb. 23, 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.

HCV tends to spread rapidly in third-world countries because of bad hygiene in

hospitals. © CSGH

" 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.

--------------------------------------------------------------------------------

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by University of Copenhagen.

--------------------------------------------------------------------------------

Journal Reference:

nne Mikkelsen, Johannes Holst, Jens Bukh, Allan Randrup Thomsen, and

Jan Pravsgaard Christensen. Enhanced and Sustained CD8 T Cell Responses with an

Adenoviral Vector-Based Hepatitis C Virus Vaccine Encoding NS3 Linked to the MHC

Class II Chaperone Protein Invariant Chain. The Journal of Immunology, January

21, 2011 DOI: 10.4049/%u200Bjimmunol.1001877

[Guest guest]

http://www.sciencedaily.com/releases/2011/02/110223122258.htm

New Vaccine Technology Protects Mice from Hepatitis C Virus

ScienceDaily (Feb. 23, 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.

HCV tends to spread rapidly in third-world countries because of bad hygiene in

hospitals. © CSGH

" 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.

--------------------------------------------------------------------------------

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by University of Copenhagen.

--------------------------------------------------------------------------------

Journal Reference:

nne Mikkelsen, Johannes Holst, Jens Bukh, Allan Randrup Thomsen, and

Jan Pravsgaard Christensen. Enhanced and Sustained CD8 T Cell Responses with an

Adenoviral Vector-Based Hepatitis C Virus Vaccine Encoding NS3 Linked to the MHC

Class II Chaperone Protein Invariant Chain. The Journal of Immunology, January

21, 2011 DOI: 10.4049/%u200Bjimmunol.1001877