A unique partnership between Syracuse University and the Serum Institute of India
could lead to better access to life-saving vaccines for children living in some of the
most impoverished areas of the world. The institute recently awarded $250,000 to a
team of SU researchers led by Robert Doyle, assistant professor of chemistry in
The
College of Arts and Sciences, to develop new oral vaccines against tetanus and
rotavirus, a severe form of diarrhea that affects infants and young children
worldwide.
Tetanus is caused by a toxin produced by bacteria naturally found in soil. The
vaccine is only available by injection. While the disease is rare in the Western world,
tetanus caused an estimated 257,000 deaths in low-income countries between 2000
and 2003, according to the World Health Organization's (WHO) latest report. A
significant percentage involved infants born in predominantly rural areas who were
exposed to the tetanus bacteria during unsanitary delivery procedures. Likewise,
infants and young children in these same countries have a much higher risk of dying
from rotavirus than those living in Western nations. The disease killed an estimated
500,000 children in developing nations during 2004, according to a 2007 WHO
report.
"We are very excited to be working with the Serum Institute of India on these
projects," Doyle says. "This is a difficult area of research due to the nature of the
molecules we will be working with. But, if we are successful, our work could have an
enormously positive impact on the lives of people well beyond Syracuse University.
This is truly Scholarship in Action."
Founded in 1966, the Serum Institute of India produces and supplies low-cost, life-
saving vaccines for children and adults living in low-income countries. It is the
world's largest producer of measles and diphtheria-tetanus-pertussis (DPT) vaccines.
An estimated two out of every three immunized children in the world have received a
vaccine manufactured by the Serum Institute.
"Our company's philanthropic philosophy is to make high-quality, affordable, life-
saving vaccines available for underprivileged children in both India and in more than
140 countries across the world," says S.V.Kapre, executive director of the Serum
Institute of India. "This new partnership with Syracuse University will help the
Serum Institute further this endeavor as it will open new doors of vaccine usage."
The institute approached Doyle because of his successful research to develop an oral
form of insulin, which may someday enable people with insulin-dependent diabetes
to take fewer daily injections. An oral vaccine for tetanus would enhance distribution
in impoverished countries. Doyle's team will also explore new ways to synthesize the
rotavirus vaccine to make it more accessible to children in developing nations.
A new laboratory has been established in SU's Center for Science and Technology for
the research, which poses a number of challenges. Similarly to insulin, the protein
molecules used in the tetanus vaccine are destroyed in the digestive system. However,
the tetanus molecules are 30 times larger than insulin, making them more difficult to
transport. The vaccine is created by boiling the tetanus bacteria in a chemical
solution, causing the protein to completely unfold. In its new, unfolded state, the
tetanus protein is harmless but is still recognized as tetanus by the immune system so
as to trigger a response that protects the person from the disease.
"It's like frying an egg," Doyle says. "The egg white, which is a protein, is clear when
you crack the egg into a pan. When the egg heats up, the egg white becomes opaque
as the protein unfolds. You still recognize it as an egg, but you can't make the egg
white clear again after it's been heated."
The challenge is to figure out how to package this large molecule, sneak it through
the digestive system unharmed, and transport it through the wall of the small
intestine where it can be absorbed into the bloodstream. "Tetanus is a strange and
wonderful molecule," Doyle says. "We need to get a better idea of what the unfolded
protein looks like and try to predict areas that would make good targets for attaching
a transport vehicle."
Problem is, you can't actually see a protein molecule or the thousands of chemical
reactions that take place within it over nanoseconds of time. However, researchers
can develop computerized models of the molecules to predict their behavior and
zoom in on possible targets. Damian Allis, research professor in the chemistry
department, will be developing models for both projects. "The simulations allow us to
view the process and identify sticky ends of the proteins that could potentially be
used as binding sites for transport molecules," Allis says.
Unlike the tetanus vaccine molecule, the rotavirus molecule Doyle's team will be
working with is not a protein; it is a viral capsule-the outer core of which is coated
with proteins. "It's a totally different problem," Doyle says. "We need to deliver the
viral capsid to the wall of the small intestine and keep it there long enough to trigger
an immune response directly in the intestine, which is the first line of defense against
the disease."
Current oral rotavirus vaccines use tiny amounts of weakened, live bacteria. The
vaccines' possible side effects limit distribution in countries where access to health
care is not readily available, according to the World Health Organization. Doyle's
aim is to develop a vaccine that does not contain live bacteria and has fewer side
effects. The results could lead to wider distribution in low-income countries,
ultimately saving hundreds of thousands of lives.
"We have some strong ideas and some good people on our team who bring very
different skill sets to these projects," Doyle says. "The University has been very
supportive of this research. Every penny of the grant will go into research. It's now up
to us. We are excited about the possibilities."
