By Caree Vander-Linden
USAMRIID Public Affairs
When Dr. Kathleen ("Kat") Cashman heard the title of the best overall scientific poster at the DNA Vaccine Congress announced in San Diego last month, her first reaction was surprise.
"I thought, wow-someone else has a poster about Lassa fever virus, too!" says Cashman with a laugh. Of course, it was her poster's title being read aloud-and Cashman, upon hearing her name, realized that she had captured the prestigious Hilleman Award, given annually in memory of Dr. Maurice Hilleman, who developed 8 of the 14 vaccines currently used in routine childhood immunizations.
Cashman, a contract principal investigator at the U.S. Army Medical Research Institute of Infectious Diseases, began working with Lassa virus in 2005, when she came to the Institute as a postdoctoral research fellow.
The virus, endemic in West Africa, causes a severe hemorrhagic fever that is 20 to 50 percent fatal in humans-and causes permanent hearing loss in about one-third of those who survive. The disease also affects health care workers in endemic areas, since they may not have access to the equipment necessary to maintain barrier nursing precautions that can keep the disease from spreading.
According to Cashman, she especially liked the idea of doing work that could benefit public health, as well as protect U.S. service members around the world from a potential biological threat. So she took on a project to develop a Lassa vaccine that relies solely on the genetic code of the virus to provide protection.
DNA vaccines are made by modifying the unique genetic material, or DNA, of an organism such as a virus. This material, when injected into a person, leads to the expression of the genes within the modified DNA-and ultimately to the production of viral proteins inside the injected cells.
As a result, the person's immune system responds in a protective manner, similar to the response that would occur during an exposure to the virus itself. Cashman's vaccine is codon-optimized, meaning the gene has been tailored to the individual species to enhance protein expression and improve efficacy. In her initial studies using guinea pigs, she was able to show that all the vaccinated animals survived challenge with lethal doses of the virus.
However, there was a clear difference in delivery methods. Animals that were vaccinated by a device that delivers the vaccine into the muscle developed fever and were slightly viremic-meaning they had measurable levels of virus in their bloodstreams. In contrast, the animals that were vaccinated through the skin-using a process called dermal electroporation, or DEP-not only survived, but developed no fever and no viremia.
Encouraged by the results in guinea pigs, Cashman designed and conducted a study from January through May 2011 to test the codon-optimized DNA vaccine in nonhuman primates (NHPs) using the DEP delivery method. Not only did all the vaccinated primates survive infection, they developed no fever and no viremia.
Taken together, these research results demonstrate the candidate vaccine's efficacy in two different animal models of Lassa fever.According to Cashman, the next steps are determining the minimum effective dose of vaccine in NHPs, developing correlates, or markers, of protective immunity that would be predictive of the vaccine's efficacy in humans and evaluating the durability of protection induced by the vaccine.
Modest by nature, Cashman seems a bit taken aback by all the attention she has received-but happy that the significance of the work is being noticed. She has plenty to keep her busy; she recently applied for a joint patent with Inovio Pharmaceuticals, the developer of the delivery system.
There is still primate data to analyze, a paper to write, and other studies to design.."This is a unique opportunity, not just to help soldiers, but to help people," she says simply.
"We have a real opportunity here to do some good."