Abstract

Ebola virus (EBOV) and related filoviruses such as Sudan virus (SUDV) threaten global public health. Effective filovirus vaccines are available only for EBOV, yet restricted to emergency use considering a high reactogenicity and demanding logistics. Here we present YF-EBO, a live YF17D-vectored dual-target vaccine candidate expressing EBOV-glycoprotein (GP) as protective antigen. Safety of YF-EBO in mice was further improved over that of parental YF17D vaccine. A single dose of YF-EBO was sufficient to induce high levels of EBOV-GP specific antibodies and cellular immune responses, that protected against lethal infection using EBOV-GP-pseudotyped recombinant vesicular stomatitis virus (rVSV-EBOV) in interferon-deficient (Ifnar-/-) mice as surrogate challenge model. Concomitantly induced yellow fever virus (YFV)-specific immunity protected Ifnar-/- mice against intracranial YFV challenge. YF-EBO could thus help to simultaneously combat both EBOV and YFV epidemics. Finally, we demonstrate how to target other highly pathogenic filoviruses such as SUDV at the root of a current outbreak in Uganda.