NIH Uses Live Viruses for Bird Flu Vaccine

December 17, 2005

Saturday December 17, 2005 12:53pm

Washington (AP) - In an isolation ward of a Baltimore hospital, up to 30

volunteers will participate in a bold experiment: A vaccine made with a live

version of the most notorious bird flu will be sprayed into their noses. First,

scientists are dripping that vaccine into the tiny nostrils of mice. It doesn't

appear harmful - researchers have weakened and genetically altered the virus so

that no one should get sick or spread germs - and it protects the animals enough

to try in people.

This is essentially FluMist for bird flu, and the hope is that, in the event of

a flu pandemic, immunizing people through their noses could provide faster, more

effective protection than the troublesome shots - made with a killed virus - the

nation now is struggling to produce.

And if it works, this new vaccine frontier may not just protect against the bird

flu strain, called H5N1, considered today's top health threat. It offers the

potential for rapid, off-the-shelf protection against whatever novel variation

of the constantly evolving influenza virus shows up next - through a library of

live-virus nasal sprays that the National Institutes of Health plans to freeze.

" It's high-risk, high-reward " research, said Dr. , who heads the NIH

laboratory where Dr. Kanta Subbarao is brewing the nasal sprays - including one

for a different bird-flu strain that appeared safe during the first crucial

human testing last summer.

" It might fail, but if it's successful, it might prevent hundreds of thousands

of cases " of the next killer flu, said.

FluMist is the nation's nasal-spray vaccine that prevents regular winter flu.

Developed largely through 's lab, it's the only flu vaccine made with live

but weakened influenza viruses.

The new project, a collaboration with FluMist manufacturer MedImmune Inc.

piggybacks cutting-edge genetics technology onto that vaccine to create a line

of FluMist-like sprays against different bird flus.

" That is a great, great idea, " said Dr. Treanor of the University of

Rochester, among the flu specialists closely watching the project.

Regular winter flu shots are made with killed influenza viruses, and the

government is stockpiling experimental bird-flu vaccine made the same way. But

those bird-flu shots don't work as well as hoped. They require an incredibly

high dose, delivered in two separate injections, to spark a protective immune

response in people.

" In theory, a live-virus vaccine might actually work better. We don't know that

because we've never tried one before, " Treanor said.

Influenza is like a magician, constantly changing its clothes to avoid

detection, thus making it difficult to develop effective vaccines.

Studding the virus' surface are two proteins called hemagglutinin - the H in

H5N1 - and neuraminidase, the " N " . They act as a wardrobe: There are 16 known

hemagglutinin versions, and nine neuraminidases.

They're also what triggers the immune system to mount an attack, particularly

hemagglutinin, the protein the body aims for when it makes flu-fighting

antibodies.

When people catch the flu, they usually get H1 or H3 flu strains, which their

bodies can recognize because variations have circulated among humans for

decades.

Occasionally, genetically unique strains emerge. Until 1997, H5 strains had

never been seen outside of birds. The virus essentially put on a coat that human

immune systems didn't recognize. The result: Since 2003, a particularly strong

H5N1 strain has infected more than 130 people in Asia, killing at least 70.

H9 and H7 strains also recently have jumped from birds to people, although so

far they haven't been nearly as dangerous.

Researchers hope to create at least one live-virus nasal spray for each " H "

subtype, a project costing about $16 million of the NIH's annual $67 million

budget for flu vaccine research.

" The hemagglutinin is the major protective antigen, so that is what we're

focusing on, " explained Subbarao, a molecular geneticist who heads the project.

First on her list are the riskiest known bird flus: H5N1, with human tests

planned for April. H9N2, which recently underwent the first round of human

testing in an isolation ward at s Hopkins Bayview Medical Center. Then an H7

strain, followed by an H6 strain believed to share genes with the H5N1.

" By no means are we confident we're picking the right strain " to make first,

because flu mutates so easily, Subbarao cautioned.

She chooses vaccine strains from those that U.S. scientists who are monitoring

influenza in Asia cull from ducks, chickens and geese, and ship home for

research.

Subbarao must customize those strains for safe vaccination: First, using a new

technique called reverse genetics, she selects genes for bird-flu H and N

antigens and removes genetic segments that make them dangerous. Then she adds

the remaining gene segments to the regular weakened FluMist virus.

Stocks of the custom virus are grown in fertilized chicken eggs. Each is then

carefully cracked by hand to drain out virus-loaded liquid that in turn is

purified and put into a nasal spray.

In a high-security section of the lab, Subbarao dons a biohazard suit and

exposes vaccinated mice to various bird flu strains.

Then it's time for human testing - in a hospital isolation ward just in case the

weakened virus could infect someone.

It shouldn't, because " those problems don't exist in FluMist, " said ,

citing studies of regular FluMist in day-care centers where youngsters routinely

pass viruses back and forth.

Some studies have found that people can shed virus shortly after receiving

regular FluMist. But, " to spread infection, you'd need much more (virus) than

replicates in the nose, " he said.

Hopkins researchers gave the first of Subbarao's vaccine candidates - the H9N2

spray - to 30 volunteers last summer. To be sure they couldn't spread the virus

by coughing or sneezing, the volunteers underwent daily tests of their noses and

throats.

The vaccine appeared safe. Scientists now are analyzing whether it also spurred

production of flu-fighting antibodies, a sign that people would be protected if

they encountered the H9N2 strain. Subbarao expects results by February.

In April, pending final Food and Drug Administration permission, Subbarao will

put an H5N1 spray to a similar test.

Here's the catch: Each flu strain has subtypes. An Indonesian version of H5N1,

for example, was recently discovered that differs from a Vietnamese strain on

which Subbarao's nasal spray - and the government's stockpiled shots - are

based. She's now testing whether her vaccine protects mice against that new

Indonesian strain.

If a novel flu strain begins spreading among people, how will Subbarao tell if

her stored nasal vaccines are a good match to fight it?

NIH also will store blood samples from the people who test those sprays. Say a

new H9 strain sparks an outbreak. That virus will be tested against those blood

samples, and NIH could predict within a day which spray candidates work. If one

does, the government could order doses manufactured from that frozen stock; if

none do, scientists would have to try to brew a new vaccine.

How quickly doses could be manufactured is a different issue. All influenza

vaccines, shots or spray, currently are brewed in chicken eggs, a time-consuming

process that other research is seeking to improve.

" These are research projects, " stresses - the nasal-spray concept could

fail.

But he's optimistic. Live-virus vaccines, he maintains, are better immune

stimulators.

http://beta.abc3340.com/news/stories/1205/286748.html

December 17, 2005

>It doesn't appear harmful - researchers have weakened and genetically altered

the virus so that no one should get sick or spread germs - and it protects the

animals enough to try in people.

I don't know how they can say this about a live nasal vaccine, weakened and

altered or not. " It doesn't appear harmful " -- is just them saying they don't

know at all whether it is or isn't. God help the poor souls who volunteer to

inhale it.

Anita

<tallynsdream@...> wrote: