A team of scientists led by Katherine Hastie and Erica Ollmann Saphire from the Scripps Research Institute recently discovered the means in which the Lassa virus uses to enter human cells, which they believe provides a blueprint to design a potential vaccine for the virus.
Lassa virus, which is part of the deal arenavirus family, causes serious cases of viral hemorrhagic fever with symptoms including vomiting, fever, muscle pains, and excessive bleeding. Approximately 1 percent of those who contract the virus will be subject to its lethal effects.
What lead the researchers to their vaccine design breakthrough was revealing a key piece of the Lassa viral structure, called the surface glycoprotein. This discovery, the researchers said, can apply for any virus within the arenavirus family.
By creating mutated versions of the important parts of the Lassa molecule, Scripps researchers were able to engineer a version of the virus surface glycoprotein that was stable enough to be observed. Prior to the development of the mutated version, they found they were not able to properly study the Lassa viral structure without its components drifting apart.
They then used their mutated viral model to identify antibodies through patient samples that could bind with the glycoprotein and neutralize the virus. After a series of tests with numerous human samples, the researchers were able to identify a neutralizing antibody found from a survivor of the virus.
The structure showed that the glycoprotein contained two subunits dubbed GP2, which forms a cone-like shape, and GP1, which sits atop the cone. GP1 binds to a host cell receptor while GP2 starts the fusion process that enters a cell. After zooming in, GP1 was shown to have a long structure hanging off its side, which researchers likened to melting ice cream dripping off a cone. This structure holds together two subunits in their profusion state.
After observing the structures even closer, the researchers discovered that three of the GP1 and GP2 pairs come together in a tripod-like arrangement, which appeared to be unique to the Lassa virus. Other viruses like HIV and influenza formed a pole-like structure and not a tripod.
The tripod arrangement could be the key discovery needed for the development of a new vaccine. The effective antibodies were found to target the spot where the three GP subunits formed by locking them together, which prevented the virus from “gearing up” to enter a cell, according to a release from Scripps.
“It was great to see exactly how Lassa was different from other viruses,” Hastie said. “It was a tremendous relief to finally have the structure.”
The researchers said the next step will be to test a vaccine that prompts the immune system to target Lassa’s glycoprotein.
“There’s a tremendous global interest,” Ollmann Saphire said. “I think the world woke up when they saw the scale of the Ebola outbreak.”