Abstract
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.
Competing Interest Statement
L.J.S, N.P.K, D.B., L.C., A.J.B., C.W. and N.B. are listed as inventors or major contributors on records of innovation at the University of Washington and an associated provisional patent application that incorporates discoveries described in this manuscript. The King and Baker laboratories have received unrelated sponsored research agreements from Pfizer and Merck respectively. B.F. is an employee of AstraZeneca, Icosavax which is developing I53-50 based nanoparticle vaccines for respiratory syncytial virus and human metapneumovirus. All other authors declare no competing interests.
