| January 15,
Smallpox as A
Weapon of Bioterrorism
Penn Researchers Receive NIH Grant to Lessen the
(Philadelphia, Pa.) -
University of Pennsylvania School of Medicine researchers
have received a grant from the National Institutes of
Health (NIH) to investigate how the U.S. could combat
a possible outbreak of smallpox. Stuart N. Isaacs, MD,
Assistant Professor of Medicine in the Penn Division
of Infectious Diseases and John D. Lambris, PhD, Professor
in the Department of Pathology & Laboratory Medicine,
will lead the research into creating new therapies to
protect against the disease. The researchers were awarded
$1.1 million for the four-year study.
"Smallpox may be largely forgotten, but it certainly
isn't gone," said Isaacs. "There is a possibility, however
slight, that terrorists could obtain the virus and release
it within the U.S."
Despite the existence of a working vaccine, smallpox
could still serve as powerful weapon for bioterrorists
interested in attacking the U.S. The U.S. population
is becoming highly susceptible since Americans are no
longer vaccinated against the disease and older people
who were previously vaccinated are losing their immunity
to the virus.
There is very little vaccine stockpiled either in the
U.S. or globally to respond to a terrorist attack, and
there is no drug currently available to treat smallpox.
Death rates from a smallpox infection among an unvaccinated
population can be as high as 30%.
Currently, vaccination remains the only way to protect
an at-risk civilian population, however, a portion of
the population can have serious complications with the
vaccine, particularly pregnant women, infants, and people
with poor immune systems. There is a treatment for these
complications, a preparation of human immune globulin
- a protein taken from healthy vaccinated people - but
it is in very short supply.
Instead, Isaacs and Lambris will develop new therapies
that target related, yet functionally distinct, virus
proteins. "We are looking at a combination punch to
knock-out the effects of the smallpox virus," said Lambris.
"We will create therapeutics which will attack two proteins
that the virus produces." One therapy would prevent
the virus from entering cells and the other will neutralize
a protein that the virus produces to bypass the human
VCP, the vaccinia complement-control protein, inactivates
the human complement system, a complex system of circulating
proteins that attack invading organisms in the human
body. The complement system serves as the first line
of defense for the immune system and when the virus
disables complement proteins, it makes it easier for
it to invade and survive in human cells. By neutralizing
VCP, the researchers hope to create a therapy that would
allow a patient's complement system to control a smallpox
The researchers are also looking at B5R, a specific
protein on the surface of the virus. The virus uses
B5R as a key to unlock the walls of human cells, and
is essential for further spreading the virus within
an infected host. The researchers plan to create therapeutics
that will attach to B5R and prevent it from functioning,
thereby disabling the virus.
"I find it morbidly ironic that smallpox, the first
disease ever to be purposely immunized against - and
successfully eradicated - might come back from the dead
to pose a threat now, " said Isaacs. "Fortunately, we
now have the tools and understanding to help take the
risk out of smallpox vaccinations and potentially combat
the threat of smallpox bioterrorism."