Dr. Maria Croyle, associate professor of pharmaceutics at The University of Texas at Austin College of Pharmacy, has received $2.6 million to develop a vaccine against Ebola virus infection.
With grants from the National Institutes of Health and the Canadian Research and Technology Initiative, Croyle will lead an international research team to study the immune responses after administering a novel vaccine either by nasal spray or tablet in pre-clinical models of Ebola infection.
The team includes researchers from Croyle’s laboratory as well as those of Dr. Gary Kobinger at the Canadian National Microbiology Laboratory in Winnipeg and Dr. David Weiner at the University of Pennsylvania.
“Ebola is one of the most lethal pathogens known to man and, although outbreaks are in limited regions, the lethality of the virus is increasing with a reported 90 percent mortality rate in some regions,” said Croyle, adding that her Canadian collaborators are international experts in Ebola infection and are some of the first responders to outbreaks around the world.
“There are no real therapeutic options available for those that are infected with the virus,” Croyle said. “Medical professionals can only treat the symptoms associated with the disease so there is a great need for something that could protect those exposed to the virus as well as prevent further replication of the virus in those with active infection.”
The proposed vaccine consists of a recombinant adenovirus, said Croyle. The genes that allow the adenovirus to cause disease are removed and replaced by gene sequences for the proteins that coat the outer surface of the Ebola virus.
“Once this virus is given as a vaccine it induces cells to produce significant amounts of these proteins, and in turn, stimulates a broad, long-term immune response against them,” she said.
Croyle also is a co-investigator of a research project led by Kobinger, which is designed to improve and refine the vaccine using molecular biology techniques targeting the immune system.
Adenovirus, said Croyle, has been used widely to deliver genes to correct genetic disease and its genetic makeup and biology are very well understood. However, one of the problems with using adenovirus in correcting genetic disease is that it is commonly found in the environment.
“This means that the immune systems of most people will recognize the virus and attack it before the adenovirus gets the chance to deliver its genetic package,” she said. “The immune response against the adenovirus limits the ability of the vaccine to be given as several booster doses as is common with many other vaccines.”
The researchers in Croyle’s lab have developed several strategies in which they can chemically modify the outside of the adenovirus and fool the immune system into allowing the virus to deliver its genetic payload in those previously exposed to the virus. This may further improve the efficacy of the vaccine in those already exposed to adenovirus.
Her expertise in the area of oral and nasal drug delivery strengthens the ability of her team to create a highly effective vaccine. Elimination of the need for needle vaccination would allow for possible self-administration during an outbreak and minimize public health concerns with respect to needle-stick induced infections.
“The adenovirus is so versatile that once we conquer Ebola, we can push on to the next pathogen by simply trading the genes for Ebola for others,” Croyle said.
