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http://www.boston.com/news/globe/health_science/articles/2004/03/09/c

hemist_finds_new_ways_to_make_vaccines/

Chemist finds new ways to make vaccines

By Jascha Hoffman, Globe Correspondent, 3/9/2004

When letters containing anthrax spores started showing up at the

Capitol building in Washington in late 2001, most people saw it as a

national crisis. Ying Wang saw it as a scientific challenge.

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She knew that the standard vaccine for anthrax was inadequate,

neutralizing its toxins but not killing the anthrax bacteria. So she

set about to find a better way to defend against the deadly spores.

The Harvard Medical School assistant professor spent the next two

years trying to design and produce special molecules that would

prompt the immune system to kill the bacteria.

Then came the big announcement last September: Wang's vaccine worked

against an anthrax-like bacteria in mice, effectively delivering a

one-two punch to not only absorb the toxin, but to kill the bacteria

that made it.

" It worked like a charm, " she said at the time.

Beyond providing a safe and effective vaccine, Wang stated in an e-

mail Monday that she believes her lab has " introduced a new concept

in vaccine design, i.e., the combination of both prophylactic and

therapeutic components, in a single vaccine. We hope that the

concept will find broad use in the development of many other

vaccines. "

Since the discovery, Wang, 35, also an associate chemist at Brigham

and Women's Hospital, has taken two months off to deliver and care

for her first child, and dug back into her lab to work on moving the

vaccine forward. If Brigham and Women's Hospital succeeds in finding

a private company to license the vaccine and win it federal approval

for human trials -- Wang said the hospital is in discussions with

two firms now -- her lab will be involved.

The anthrax vaccine is Wang's second major scientific achievement

since 1995 when she graduated from Michigan State University and

joined the Channing Laboratory, a multidisciplinary division of

Harvard Medical School and Brigham and Women's Hospital, charged

with investigating bacteriology, chronic disease and virology.

In 2000, Wang -- with the help of her husband, Roehrl, a

research assistant at Harvard Medical School -- made waves by

suggesting a potential new cause of arthritis.

Rheumatoid arthritis is an autoimmune disease that causes the body

to break down its own cartilage, causing stiffness, pain, and

swelling. Most of the research into the disease, which affects more

than 2 million people in the United States, tries to isolate

proteins responsible for the destructive immune response. Proteins,

however, are not the only autoimmune culprits.

Carbohydrates can also trigger an immune response, Wang knew from

years of biochemical research. She became intensely curious about a

particular kind of carbohydrate found in joints, called

glycosaminoglycans, or GAGs. What she found came as a big surprise

to her and other researchers: Mice injected with GAGs showed

arthritic symptoms, and people with rheumatoid arthritis had high

concentrations of GAGs in their connective tissues and joint fluid.

" Up to our study, it was almost exclusively believed that proteins

in our body are exclusively responsible " for rheumatoid arthritis,

she said Monday. " I think it is important when studying multifaceted

diseases such as autoimmunity to maintain a broad approach and study

possible factors on a basis that is as inclusive and comprehensive

as possible. Often that requires freeing one's mind from a currently

dominating belief. That's what we have been trying to do here. "

Mekalanos, professor and chairman of microbiology and molecular

genetics at Harvard Medical School, said when her study was

published that it " suggests plausible models for how bacterial

infection might trigger arthritis and how we might go about

reversing this debilitating condition with new therapies. "

In addition to continuing work on the anthrax vaccine, Wang's small

lab is now searching for ways to eliminate GAGs, or at least block

them from binding with immune cells, in the hopes of finding a cure

for arthritis.

Wang's focus on carbohydrate-related immune response is

unconventional, but may have potential, said Dr. Bruce N. Cronstein

of New York University, who studies the ways the human body uses and

misuses swelling to fight disease.

" This hasn't yet made a big splash in the arthritis world, "

Cronstein said. " But it may well turn out to be important. "

Wang, raised in the Hu Bei province of central China, once scored

third in China's nationwide high-school math competition. She

eventually switched to biochemistry because it was more practical,

but said math is essential to her systematic approach to the study

of human pathogens.

At Harvard, Wang started out designing vaccines for everyday

infections like strep and staph. She learned to approach vaccine

design from a rational perspective, using biochemical savvy and

powerful computer models to figure out what antigens have a good

chance of working.

The first step is to understand the pathogens that cause the disease

she's targeting. The next step is to decide out which immune

responses she wants to use to fight those pathogens. And only then

can she try to design an antigen that will elicit those immune

responses in people.

" You don't just go fishing, " she said.

© Copyright 2004 Globe Newspaper Company.

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