A 10–year Lassa virus research project has yielded structural and functional details of a key viral surface protein that could help advance development of Lassa vaccines and antibody–based therapeutics, which are currently lacking. The work was led by the Scripps Research Institute (TSRI).

Knowing the structure of a virus surface molecule called the Lassa glycoprotein precursor complex (GPC) may be important to developing a vaccine. GPC mediates viral binding to and entry into cells and is a prime target for immune responses generated by a vaccine. Until now, no structure model existed for any virus in the arenavirus family because of the instability and diversity of the GPC protein. Over the past decade, TSRI scientists and their collaborators have explored the GPC, ultimately learning to stabilize the protein to determine its molecular structure. Now, scientists from TSRI, Tulane University, and Kenema Government Hospital in Sierra Leone have re–engineered the GPC and used it to study antibodies from human survivors.

Their research provides the first detailed view of the Lassa GPC bound to a human neutralizing antibody from an African survivor. This high–resolution structure reveals how the molecule is assembled and that the most effective antibodies interact only with a fully assembled GPC. The structure also shows how the molecule can be stabilized to better elicit protective antibodies. The availability of this structure may facilitate development of vaccines or antibody–based therapeutics.

The article titled, "Structural basis for antibody–mediated neutralization of Lassa virus," was published in the journal Science.