Design of universal Ebola virus vaccine candidates via immunofocusing

• DOI: 10.1073/pnas.2316960121
• Publication Date: 2024-02-06T18:36:19Z
• Authors: Duo Xu; Abigail E. Powell; Ashley Utz; Mrinmoy Sanyal; Jonathan Do; J. J. Patten; Juan I. Moliva; Nancy J. Sullivan; Robert A. Davey; Peter S. Kim
• Keywords: Ebola vaccine; Filoviridae; VP40

The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved prevent disease, they are distributed the limited ring vaccination setting only indicated for prevention of infection from orthoebolavirus zairense (EBOV)—one three species that caused previous outbreaks. glycoprotein GP mediates serves as primary target neutralizing antibodies. Here, we describe universal vaccine approach using structure-guided design candidates with hyperglycosylation aims direct antibody responses away variable regions toward conserved epitopes GP. We first determined landscape on used generate hyperglycosylated variants four additional glycosylation sites mask highly glycan cap region. then created by displaying wild-type or ferritin nanoparticles (Fer). Immunization these antigens elicited potent antisera against EBOV mice. Importantly, observed consistent cross-neutralizing activity Bundibugyo Sudan GP-Fer glycans. In comparison, elicitation was rare mice immunized GP-Fer. These results demonstrate potential strategy develop confer cross-protective immunity existing emerging filovirus species.