A conversation in China leads to
successful research collaboration
What began as a casual conversation last summer between between two members
of the Yale delegation to China has resulted in a successful collaboration
between two scientists who otherwise might never have met.
While enjoying breakfast one morning in Beijing, doctoral student Stacey Demento
and Professor Erol Fikrig (see related story) began chatting about their
respective areas of research.
Demento is studying at Yale with Tarek Fahmy, an assistant professor in biomedical
engineering. In her research, she is working to develop bacterial-mimicking biodegradable
nanoparticles as a way to use oral vaccines as delivery systems for bacterial-mimicking
biodegradable nanoparticles.
“In the most basic terms, I disguise vaccines as bacteria to trick the
immune system,” Demento explains.
She does this by loading an antigen — part of an infectious disease agent
that cannot cause the disease itself but does stimulate a response by the body’s
immune system — into polymer nanoparticles. She then coats the surface
of the nanoparticle with a molecule called lipopolysaccharide (LPS), which is
found in the cell wall of some bacteria.
“LPS is a potent stimulator of the immune system,” says Demento. “Immune
cells recognize and internalize nanoparticles coated with LPS as if the particles
were bacteria. In other words, the vaccine is gaining entry into an immune cell
by the same mechanism as an infectious agent.”
In his conversation with Demento, Fikrig learned that Demento was using a model “dummy” antigen
to test and improve her nanoparticles vaccine delivery system. Fikrig is chief
of the Infectious Diseases Section at the School of Medicine, and is studying
an array of vector-borne diseases. He suggested that she instead use a protein
from the West Nile Virus that his laboratory had already successfully tested
in a vaccine using a traditional method of injection in mice and horses.
When the two returned from China, they met with Fahmy to plan an initial experiment.
Demento worked with Harald Foellmer, a research scientists in Fikrig’s
laboratory, to vaccinate mice by subcutaneous (beneath the skin) or oral administration.
Four weeks later, they exposed the mice to West Nile virus.
“I’m very happy to report that on the first run, all 10 of the subcutaneously
vaccinated mice survived infection, while surprisingly only two of the orally
immunized mice did not survive,” says Demento, noting that an oral vaccine
would be a preferable delivery system for this type of antigen.
With some improvements, she notes, “we have reason to believe that oral
and nasal vaccination with these particles could be completely successful in
future experiments.” In fact, subsequent studies have already proved promising,
she adds.
“Currently, no vaccine or specific treatment for West Nile virus is available,
and we feel that this approach may offer a successful clinical application,” says
Demento. “We now have an application to prove that our nanoparticles provide
a functional protection in an important disease model.”
She adds, “The Yale 100 trip to China was filled with great opportunities
and catalyzed an exciting project between nanotechnology and medicine.”
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