Ebola virus vaccine(National Institute of Allergy & Infectious Diseases)

Filoviruses, including Ebola and Marburg viruses, present significant global health challenges due to their high mortality rates. Despite the availability of several Ebola virus vaccines, none provide cross-protection against multiple filovirus species. In this study, we developed recombinant live attenuated measles virus-based vaccine candidates designed to express Ebola or Marburg virus glycoproteins and generate virus-like particles for pan-filovirus immunization. The administration of these candidates by intraperitoneal injection into IFNAR^-/- mice elicited robust antibody and cellular immune responses specific to Ebola and Marburg virus glycoproteins, with virus-like particles expressing candidates inducing the strongest immunity. Importantly, all vaccines containing Ebola virus glycoproteins afforded complete protection against mouse-adapted Ebola virus; meanwhile, those with Marburg glycoproteins provided protection against lethal replication competent vesicular stomatitis virus-Marburg virus challenges. These findings support the potential of measles virus-based vectors and virus-like particles as promising platforms for the development of vaccines targeting multiple filoviruses.

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