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 predominately 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 under-privileged 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 literally 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."