In a pioneering discovery, researchers have determined that a human antibody strongly neutralises a type of lethal dengue virus in animals. The result can lead to the first effective therapies and vaccines against dengue, a complex of four distinct but related mosquito-borne viruses that infect about 390 million people a year globally.
"This human antibody not only kills dengue virus but also prevents enhanced dengue disease," said James Crowe Jr, co-corresponding author from Vanderbilt University situated in Tennessee.
The researchers previously generated human antibodies in the lab against a complex antigenic portion of the viral envelope. They froze samples at very low temperatures so they could visualise antibody-antigen binding almost down to the atomic level. The team was able to identify a human monoclonal antibody against dengue virus type 2 (DENV2) that "locked" across an array of envelope proteins. In a mouse model, this prevented the virus from fusing to its target cell, thus it prevents infection.
The antibody has a second major function - it blocks the binding of the other class of antibodies that otherwise would enhance infection. "It is a potential target for the development of dengue vaccines and therapeutics," the researchers said.
The four "serotypes" of dengue are distinguished by different antigens or proteins on the viral envelope that elicit immune responses. What makes dengue so challenging and so dangerous is that antibodies generated against one "serotype" do not protect against the others. In fact, they actually can enhance infection by a second serotype.
Sequential infections increase the risk for dengue hemorrhagic fever and dengue shock syndrome, characterised by fever, vomiting, internal bleeding and potentially fatal circulatory collapse. The paper appeared in the journal Science.