In developing their new ebolavirus vaccine design, Zhu and his team focused on the relative instability of the glycoprotein structure as a potential factor in vaccine efficacy. They studied in detail the molecular sources of this instability and eventually devised a series of modifications that greatly stabilize the glycoprotein.
In mice and rabbits, their modified glycoprotein elicited a more potent neutralizing antibody response against two different ebolaviruses--the Makona strain of Ebola virus and the Ugandan strain of Bundibugyo ebolavirus--and compared those with the wild-type glycoprotein.
"Think of our nanoparticle as your sports vehicle, with a rack that carries a mountain bike and a trunk where you store clothes, tools and food," explains Zhu. "The only difference here is that the Ebola virus spike is your mountain bike, and the blocking domains and T-cell epitopes are your things in the trunk. We call it multilayer design.".
"There are many things in the field of Ebola virus vaccine that still need to be carefully examined, but in this study, we have arrived at two nanoparticle-based designs that seem very suitable for further optimization and testing," says Zhu.
He says the vaccine approach can be extended to other members of the same virus family, such as Marburg virus. Ebolaviruses and marburgvirus both belong to a group of viruses, known as filoviruses, which have a bizarre filiform shape when viewed under a microscope.
