Re: Scientists Find Promising Vaccine Targets On Hepatitis C Virus

[Guest guest]

But they STILL are not doing any public service announcements to let

everyone know if they received blood or blood products prior to 1992

or if they did drugs and shared needles that they should be tested

for Hepatitis C.  1992 + 30 = 2022, so between then and now how many

more people are going to get diagnosed with both Cirrosis of the

Liver Stage 4 and Hepatitis C at the same time?  Will the vaccine

still work even though so much damage has already been done?

I just am so

happy that they are coming out with a vaccine. So many lives

will be saved because of the vaccine!

Love

Janet

 

"There are souls in this world that have the gift of

finding joy everywhere and of leaving it behind them when they

go"

Frederick Faber

 

 

From:

"beastman@..."

To:

Hepatitis C <Hepatitis_C_Central >

Sent:

Sunday, April 8, 2012 11:27 AM

Subject:

Scientists Find Promising Vaccine

Targets On Hepatitis C Virus

 

Scientists Find Promising Vaccine Targets On

Hepatitis C Virus

05 Apr 2012

A team led by scientists at The Scripps Research

Institute has found antibodies that can prevent

infection from widely differing strains of hepatitis

C virus (HCV) in cell culture and animal models.

HCV's very high rate of mutation normally helps it

to evade its host's immune system. The newly

discovered antibodies, however, attach to sites on

the viral envelope that seldom mutate. One of the

new antibodies, AR4A, shows broader HCV neutralizing

activity than any previously reported anti-HCV

antibody.

"These antibodies attach to sites on the viral

envelope that were previously unknown, but now

represent promising targets for an HCV vaccine,"

said Mansun Law, an assistant professor at Scripps

Research. Law is the senior author of the new

report, which appears online this week in the

Proceedings of the National Academy of Sciences.

A Desperate Need

An effective HCV vaccine is desperately needed. The

World Health Organization (WHO) estimates that the

virus has established mostly silent infections in

130 to 170 million people worldwide - nearly 3

percent of the human population - and spreads to 3

to 4 million new people annually. HCV principally

infects liver cells, and is thought to cause

chronic, often-unnoticed liver inflammation, which

eventually can lead to serious liver ailments. The

virus already is responsible for about a quarter of

annual US cases of liver cirrhosis and primary liver

cancer, and it is the leading cause of liver

transplants. In some developing countries, HCV

prevalence is extremely high; studies suggest that

in Egypt, as many as 22 percent of the population is

infected - apparently due to poor screening of blood

products and past re-use of syringes. Even in

developed countries, HCV infections represent a

looming public health crisis. In the United States

and Europe, up to 14 million people are now

HCV-positive, and each year an estimated 150,000

people are newly infected.

The current leading treatment for HCV infection

involves a 12- to 36-week course of the

immune-stimulating protein interferon-alpha, the

antiviral drug ribavirin and HCV protease blocker.

But it is not completely effective, and it causes

significant adverse side effects - aside from being

very expensive. To fully stamp out the HCV pandemic,

especially in developing countries, scientists will

have to develop a cheap preventive vaccine.

Yet an effective HCV vaccine has so far been

elusive. The virus mutates very rapidly, and thus,

antibodies raised against one isolate of HCV

typically won't protect against a subsequent HCV

infection. Hospital samples of HCV suggest that the

virus's genes, and the proteins for which they code,

are highly variable even within an individual

patient.

"One of the big goals of HCV vaccine development has

been to find an accessible spot on the virus that

doesn't change constantly," said Law.

Searching for Vulnerabilities

To find such vulnerable spots, researchers sift

through antibodies sampled from infected people and

look for those antibodies that can neutralize a

broad range of viral strains. The locations on the

virus where those broadly neutralizing antibodies

bind mark the vulnerable viral structures that can

be used as the bases of a broadly effective,

antibody-stimulating vaccine. Previous studies,

including a 2008 study in Nature Medicine, for which

Law was lead author, have found some broadly

neutralizing HCV antibodies. But for the present

study, Law and his colleagues used a more thorough

approach, known as "exhaustive panning," to see if

they could find new and even more broadly

neutralizing antibodies. "Exhaustive panning is a

powerful technique for finding rare antibodies that

might otherwise go undetected," Law said.

HCV employs a complex of two envelope glycoproteins,

E1 and E2, to grab and fuse with target cells. k

Giang, a research assistant in Law's lab, harvested

this viral E1-E2 complex from HCV-producing cells in

a lab dish and used it as "bait" for a panel of

antibodies derived from the blood of a person with

chronic HCV infection. The exhaustive panning

technique involves exposing this bait protein to

different anti-HCV antibodies in sequence, so that

the known antibody-binding sites on the complex are

progressively covered until only new ones are left.

In this way, Giang catalogued 73 new anti-HCV

antibodies, which bind to five distinct "antigenic

regions" on the E1-E2 complex. In standard cell

culture tests of HCV-neutralizing ability, several

of these antibodies showed an ability to neutralize

infection by a wide range of HCV strains. One, AR4A,

turned out to bind to an almost-unvarying spot on

E1-E2 complex, close to the surface of the virus's

outer coat of fat molecules. AR4A showed significant

neutralizing ability against all 22 HCV strains in a

test panel - not only in tests in Law's lab, but

also in confirmatory tests at the University of

Copenhagen.

The Broadest Neutralizing Activity Yet

The new antibody thus is more broadly protective

than the previous top contender, AR3A, which Law

described in his 2008 Nature Medicine paper. "This

human antibody AR4A has the broadest

HCV-neutralizing activity known to the field," Law

said.

Collaborating researchers at Rockefeller University,

who recently engineered a line of HCV-infectable

mice, showed that AR4A antibodies protected these

mice from two widely different HCV strains. A

combination of half-doses of AR3A and AR4A

antibodies worked less well.

The next step for Law and his colleagues is to start

making and testing prototype vaccines based on the

vulnerable HCV binding sites that have been revealed

by these antibody studies. The researchers also plan

to use the new antibodies to study the structure and

function of HCV proteins such as the all-important

E1-E2 complex.

Anti-HCV antibodies such as AR4A and AR3A could have

some therapeutic use, too. Although they wouldn't be

able to clear existing HCV infections and would be

too expensive and difficult to use on a large

population to prevent new infections, they could be

useful in preventing new HCV liver infections in

liver transplant patients. Such infections can

spread from HCV reservoirs in the patient's body to

the newly transplanted liver tissue.

"Antibody-based treatment has worked extremely well

for liver transplants to patients with hepatitis B

virus, and we hope the new HCV antibodies can be

just as helpful to HCV liver transplant patients,"

Law said.

..

--

Bill Eastman

www.ke5asu.com/links.html