Abstract
AbstractEbola 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 the 2022 outbreak in Uganda.
Funder
KU Leuven
EC | Horizon 2020 Framework Programme
Flemish Research Foundation (FWO) Excellence of Science (EOS) program
V.L. acknowledges a research assistant fellowship from KU Leuven
J.M. grant support from the Chinese Scholarship Council
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Infectious Diseases,Pharmacology,Immunology
Reference59 articles.
1. Malvy, D., McElroy, A. K., de Clerck, H., Günther, S. & van Griensven, J. Ebola virus disease. Lancet 393, 936–948 (2019).
2. Huber, C., Finelli, L. & Stevens, W. The economic and social burden of the 2014 Ebola outbreak in West Africa. J. Infect. Dis. 218, S698–S704 (2018).
3. Henao-Restrepo, A. M. et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet 389, 505–518 (2017).
4. WHO. Preliminary results on the efficacy of rVSV-ZEBOV-GP Ebola vaccine using the ring vaccination strategy in the control of an Ebola outbreak in the Democratic Republic of the Congo: an example of integration of research into epidemic response. https://www.who.int/publications/m/item/preliminary-results-on-the-efficacy-of-rvsv-zebov-gp-ebola-vaccine-using-the-strategy-in-the-control-of-an-ebola-outbreak (2019).
5. Agnandji, S. T. et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe. N. Engl. J. Med. 374, 1647–1660 (2016).