Exposure through contact with rodents that carry the virus or from human-to-human transmission produces fever or malaise in 80% of those infected, but also promotes deadly hemorrhagic fever, neurological problems or shock in a smaller proportion. In fact, the CDC estimates that of the 100,000 to 300,000 individuals who contract Lassa yearly, nearly 5000 will die.
Early treatment with the anti-viral drug ribavirin is moderately effective at treating Lassa disease. Nonetheless, nearly a quarter of 600 individuals infected died after a serious Lassa outbreak in early 2019 in Nigeria, highlighting need for more effective treatment options or better yet a means of prevention, such an anti-Lassa vaccine, which currently does not exist.
Scientists at LJI apply studies of protein structure to the design of novel vaccines, with a focus on Lassa and other diseases that pose global health problems. Two years ago structural immunologist Erica Ollmann Saphire, PhD, a world leader in that effort, was the first to report the molecular structure of a Lassa virus glycoprotein in direct protein-protein contact with an antibody identified in the blood of a patient who had survived the disease. That snapshot revealed how an apparently effective anti-Lassa antibody latched onto a glycoprotein decorating the surface of the virus and halted infection. That analysis also suggested how antibodies could be genetically modified to create a “pan-Lassa” antibody capable of recognizing more than one of the four Lassa virus strains. Saphire recently extended structural analysis of the same glycoprotein “epitope” in contact with low, medium, and high-affinity antibody candidates, as a side-by-side comparison of molecular attributes displayed by maximally protective antibodies.
Structural analyses of physical virus/antibody contact points guide efforts to combat infectious diseases like Lassa on two distinct fronts. First, they provide molecular instructions for how to engineer therapeutic monoclonal antibodies that could potentially be infused into patients who already have the disease. Secondly, they illustrate how to “present” the target glycoprotein immunogen in 3-D space in a manner that would elicit a potent immune response against the virus as a prototype for a future vaccine.