USAMRIID received one of three top poster awards at the 2011 Chemical and Biological Defense Science and Technology Conference sponsored by the Defense Threat Reduction Agency held in Las Vegas, Nevada, in November.

Dr. Les Dupuy, a contract principal investigator in the Institute's Virology Division and colleagues at EpiVax, Inc. of Providence, Rhode Island, described a promising avenue for vaccine development using immunoinformatics'a technique that uses computerized analysis of biological data to tackle a problem related to the human immune system.

In this case, the "problem" is three related viral subtypes'Venezuelan, Eastern, and Western equine encephalitis viruses (VEEV, EEEV and WEEV, respectively). All are categorized as Class B biological threat agents due to their ability to cause disease in humans, as well as their potential ease of production, stability, and infectivity by the aerosol route. Dupuy's work could pave the way for development of a broadly protective vaccine against all three viruses.

Currently, a live attenuated vaccine for VEEV (made with a weakened form of the virus) is available for limited use as an Investigational New Drug, but is not well tolerated by many recipients. Other investigational vaccines for VEEV, EEEV and WEEV, made with formalin to inactivate the virus, are less effective in producing an immune response. Development of next-generation vaccines to protect against these infections is, therefore, a high priority.

Dupuy explained that when a virus invades a human host, the immune system immediately takes over and begins to try to overcome the invader. Key to the immune system is the body's ability to distinguish between its own cells, or "self" and foreign cells, or "nonself." When the immune system encounters "nonself" cells, it immediately launches an attack. A microbe or molecule that can trigger this process is called an antigen'and an epitope is simply the localized region on the surface of an antigen that is capable of eliciting a specific immune response.

Dupuy and colleagues at USAMRIID and EpiVax had already looked at the genetic makeup of VEEV and developed DNA vaccines based on epitopes recognized by T cells'the white blood cells that play an important role in ridding the body of infection. They also had done some preliminary testing of these vaccines in mice, which demonstrated the potential of this approach.

Using a prediction algorithm developed by EpiVax, the epitopes that were most likely to elicit an immune response in humans were identified in the structural proteins from140 different strains of VEEV, EEEV, and WEEV. Essentially, the technique could allow scientists to whittle down the genetic sequence to only the "pieces" that are needed to provide protection.

"We believe the combination of multiple T cell epitopes from VEEV, EEEV and WEEV will result in a highly effective vaccine that could protect against infection from all three viral subtypes," Dupuy commented. The team's next step is to test the efficacy of this vaccine candidate in mouse models of infection.

This pilot project was funded through a Translational Immunology Research and Accelerated Development grant to the University of Rhode Island from the National Institute of Allergy and Infectious Diseases.