By Irnela Bajrovic
When the 2014 Ebola outbreak ravaged the African west coast, there was a sense of panic that swept the global community. I wondered how a disease with truly gruesome symptoms, such as hemorrhaging from all orifices on the body, could not have an effective vaccine to protect the world’s population. Furthermore, it bothered me that very few vaccine development projects address the practicality of their use in the developing world, especially since several outbreaks originate in those very regions.
While there are various candidates currently being tested in clinical trials for protection against Ebola virus, they all require storage at ultra-low temperatures, an unrealistic requirement for rural Guinea, Liberia, and Sierra Leone—the three countries severely affected by the outbreak. That is why Maria Croyle, Ph.D., Stephen Schafer, and I decided to take this challenge head on.
Since recent work from our laboratory at the University of Texas at Austin showed that a single dose of a formulated respiratory vaccine fully protected nonhuman primates from a lethal dose of Ebola, it was clear that the vaccines currently on the market could be redesigned to better suit the developing world. We have taken to stabilizing a recombinant adenovirus-based vaccine in a thin film for self-immunization by the oral route.
Recombinant adenovirus expressing the E coli. beta-galactosidase transgene was dissolved in preparations consisting of three different concentrations of a standard base formulation mixed with two different binding agents and a plasticizing agent, each dissolved in three different solvent systems, in a partial 4×6 factorial design. Recovery of infectious virus from each of the 18 formulations, both before and after drying, was then tested using viral titer, which was visualized by histochemical staining. Dry time, dissolution rates, water content, and pH were also observed.
Optimal formulations were dry within 5 hours, experiencing a minimal pH drop from 7.5 to 6.0, dissolved in 1 to 2 minutes, had water content ranging from 1% to 6%, and had viral recovery rates of about 90%. Future studies will evaluate long term stability and physical properties of infectious virus in the 18 formulations under conditions that are experienced in Africa, and use them in several animal models of infectious disease. The target vaccine will no longer require extremely low temperatures to remain effective during storage for long periods of time, therefore becoming exponentially more practical for regions without constant and reliable electricity.
To learn more about our discoveries, check out our poster session on Thursday, October 29, from 8–11 am.