Researchers find new target for dengue virus vaccine

Researchers at the University of North Carolina used an experimental technique to show a vulnerability in the dengue virus, according to a study recently published in Proceedings of the National Academy of Sciences.

The scientists used a technique new to the dengue field to reveal a molecular hinge where two regions of a protein connect in dengue type three. The study showed that after primary infection, most human antibodies that neutralize the virus bind to that hinge region.

The study was the first to demonstrate how these binding sites can be genetically swapped out for amino acids from another dengue type without altering the integrity of the virus.

"This gives us a lot of insight into how human antibodies work," Aravinda de Silva, one of the study's authors, said. "And there could be a lot of translational aspects to this; it could lead to a new way to create vaccines for other diseases."

Making an effective vaccine against dengue has been difficult because of a phenomenon called antibody dependent enhancement. When individuals infected with one type of dengue develop a natural immune response, they become more susceptible to a more severe infection when they encounter a second type of dengue. As a result, a vaccine offering immunity for one type of dengue could make other types of dengue more virulent and deadly.

The researchers developed strategies to replace the epitope hinge of dengue virus type three with a hinge from dengue type four. The team determined that antibodies targeting dengue virus type four were able to neutralize the new hybrid virus.

"This told told us that the epitope we thought was important was indeed the main site for antibody binding," de Silva said. "If antibodies had been able to bind to other sites on the virus, then we would have seen a small drop in protection against dengue three. Instead, we saw a complete loss of protection."

The researchers are conducting similar experiments with dengue one and dengue three and plan to use their results to study why antibodies bind to a certain epitope but not to other sites. The information could lend more insight into how to design effective dengue vaccines.