Dengue virus advance paves way for vaccination
MedWire News: US researchers have identified the antibodies responsible for the neutralization of the dengue virus and their target viral epitopes.
Using blood cells from local travelers infected with the virus, the scientists showed that the dengue-specific human antibody response consists of distinct populations of serotype cross-reactive and type-specific antibodies.
Type-specific antibodies are responsible for the neutralization of the virus, whereas cross-reactive antibodies play a minor role.
"Our study for the first time shows what region the immune system of humans target when they are fighting off the virus," stated Aravinda de Silva (University of North Carolina, Chapel Hill) in a press release.
Writing in the Proceedings of the National Academy of Sciences, de Silva and colleagues note that individuals infected with the dengue virus develop potent serotype-specific neutralizing antibodies that can be detected more than 60 years after infection.
The epitopes involved by the neutralizing antibodies have not been identified, however; this is "a significant knowledge gap impeding the current global effort to develop dengue vaccines," say the researchers.
In a mouse model, the neutralizing monoclonal antibodies to the dengue virus recognize epitopes that are present on the recombinant dengue virus envelope (E) proteins.
Characterizing human sera and human monoclonal antibodies, the researchers observed that the majority of neutralizing antibodies in human immune sera bind to intact virions and not to the E proteins alone. Two of the three strongest neutralizing human monoclonal antibodies bound to the E protein isotopes were preserved in the virion, but not on the recombinant E protein.
These findings were confirmed with newly generated monoclonal antibodies derived from dengue virus-immune individuals.
Based on the results of antibody depletion studies, "we suggest that the packing of E proteins on the virion surface creates unique epitopes involving two or more E protein molecules in adjacent symmetry groups," write de Silva and colleagues.
The group believes the antibodies neutralize the infection by binding to the epitope that is expressed only when the E proteins are assembled on the virus particle. These quaternary epitopes are the targets of the human neutralizing antibody response.
Studies published last year showed that antibodies recognize similar complex epitopes in both HIV and West Nile Virus, note the researchers.
The results, they add, have important implications for the development of dengue virus vaccines. Studies are needed to determine if these live viral vaccines can induce neutralizing antibodies that bind to the epitopes expressed on the virion.
By MedWire Reporters