New research led by scientists at California’s La Jolla Institute for Immunology (LJI) reveals the workings of a human antibody called mAb 3A6, which may prove to be an important component for Ebola virus therapeutics.
This antibody was isolated from blood samples from an Ebola survivor treated at Emory University Hospital during the 2014-2016 Ebola virus outbreak, an outbreak that began in West Africa and killed more than 11,300 people.
In their new study, the researchers showed that mAb 3A6 helps block infection by binding to an important part of Ebola's viral structure, called the ‘stalk’. Study collaborators at the NIH's National Institute of Allergy and Infectious Diseases (NIAID) found that treatment with mAb 3A6 can benefit non-human primates in advanced stages of Ebola virus disease.
"This antibody offers the best protection in primates, at the lowest dose yet seen for any single antibody," says LJI Professor, President and CEO Erica Ollmann Saphire PhD MBA, who led the recent Nature Communications study alongside John A G Briggs Ph.D of Cambridge University and the Max Planck Institute of Biochemistry; Gabriella Worwa DVM, and Jens H Kuhn MD PhD of NIAID; and Carl W Davis PhD and Rafi Ahmed PhD, of the Emory Vaccine Center.
The discovery that mAb 3A6 appears effective at a very low dose is also exciting. "The lower the amount of an antibody you can deliver to someone, the easier it will be to manufacture a treatment - and the lower the cost," says study first author Kathryn Hastie PhD, LJI Instructor and Director of LJI's Center for Antibody Discovery.
The key to treating Ebola virus is to find antibodies that anchor tightly to and block essential machinery of the virus. The researchers zeroed in on mAb 3A6 because it appears to target a structure on Ebola virus called the ‘stalk’. The stalk is an important part of the Ebola virus structure because it anchors Ebola's glycoprotein structure (which drives entry into a host cell) to Ebola's viral membrane.
The team spearheaded efforts to capture images of mAb 3A6 in action. The researchers used two imaging techniques, called cryoelectron tomography and X-ray crystallography, to show how mAb 3A6 binds to Ebola virus to interrupt the infection process.
In the illustration above, the model on the left shows how the Ebola virus stalk has a compact conformation, which blocks the site where mAb 3A6 would bind. The model on the right shows how this portion of the stalk can adopt an extended, or lifted, conformation, which would allow mAb 3A6 to access its binding domain.
- Hastie KM, Salie ZL, Ke Z, et al. Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP(1,2) in a position elevated from the virion membrane. Nat Commun. 2025;16(1):1293. doi:10.1038/s41467-025-56452-2