A Multivalent Pan-Ebolavirus Nanoparticle Vaccine Provides Protection in Rodents from Lethal Infection by Adapted Zaire and Sudan Viruses

Both Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) are members of the family Filoviridae, first discovered in 1976 during outbreaks of hemorrhagic fever in northern Zaire and southern Sudan. Ebola virus disease outbreaks are major public health events because of their potential for human-to-human transmission with high case fatality rates. Filoviral surface glycoproteins (GPs) are known to be the primary targets of neutralizing antibodies for protection from disease, and are the relevant immunogens in the two approved EBOV vaccines. Here we describe the design, electron microscopy-based structural characterization, and efficacy testing of a series of icosahedral I53-50 nanoparticles displaying prefusion trimeric EBOV and SUDV GP antigens. Mice and guinea pigs vaccinated with either a cocktail of EBOV-GP-I53-50 plus SUDV-GP-I53-50 or mosaic EBOV / SUDV-GP-I53-50 nanoparticles were protected from death or severe clinical signs of disease and weight loss, respectively, when challenged with either mouse-adapted EBOV or guinea pig-adapted SUDV.