Single-dose YF17D-vectored Ebola vaccine candidate protects mice against both lethal surrogate Ebola and yellow fever virus challenge

Lemmens, V.; Kelchtermans, L.; Debaveye, S.; Chiu, W.; Vercruysse, T.; Ma, J.; Thibaut, H. J.; Neyts, J.; Sanchez-Felipe, L.; Dallmeier, K.

doi:10.1101/2023.01.13.523888

bioRxiv · 10.1101/2023.01.13.523888

Single-dose YF17D-vectored Ebola vaccine candidate protects mice against both lethal surrogate Ebola and yellow fever virus challenge

Lemmens, V.·Kelchtermans, L.·Debaveye, S.·Chiu, W.·Vercruysse, T.·Ma, J.·Thibaut, H. J.·Neyts, J.·Sanchez-Felipe, L.·Dallmeier, K.

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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.

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Lemmens, V., Kelchtermans, L., Debaveye, S., Chiu, W., Vercruysse, T., Ma, J., Thibaut, H. J., Neyts, J., Sanchez-Felipe, L., Dallmeier, K.. 2023-01-13. Single-dose YF17D-vectored Ebola vaccine candidate protects mice against both lethal surrogate Ebola and yellow fever virus challenge. https://doi.org/10.1101/2023.01.13.523888

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