Lemmens Viktor, Kelchtermans Lara, Debaveye Sarah, Chiu Winston, Vercruysse Thomas, Ma Ji, Thibaut Hendrik Jan, Neyts Johan, Sanchez-Felipe Lorena, Dallmeier Kai
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Virology and Chemotherapy, Molecular Vaccinology & Vaccine Discovery, BE-3000, Leuven, Belgium.
KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Translational Platform Virology and Chemotherapy (TPVC), BE-3000, Leuven, Belgium.
NPJ Vaccines. 2023 Jul 11;8(1):99. doi: 10.1038/s41541-023-00699-7.
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 the 2022 outbreak in Uganda.
埃博拉病毒（EBOV）以及诸如苏丹病毒（SUDV）等相关丝状病毒威胁着全球公共卫生。有效的丝状病毒疫苗仅适用于埃博拉病毒，但鉴于其高反应原性和苛刻的物流条件，仅限于紧急使用。在此，我们展示了YF-EBO，这是一种以黄热病毒17D（YF17D）为载体的活病毒双靶点候选疫苗，表达埃博拉病毒糖蛋白（GP）作为保护性抗原。与亲本YF17D疫苗相比，YF-EBO在小鼠中的安全性进一步提高。单剂量的YF-EBO足以诱导高水平的埃博拉病毒GP特异性抗体和细胞免疫反应，在干扰素缺陷（Ifnar）小鼠中，使用埃博拉病毒GP假型重组水疱性口炎病毒（rVSV-EBOV）作为替代攻击模型，可保护小鼠免受致死性感染。同时诱导的黄热病毒（YFV）特异性免疫可保护Ifnar小鼠免受颅内YFV攻击。因此，YF-EBO有助于同时应对埃博拉病毒和黄热病毒疫情。最后，我们展示了如何在2022年乌干达疫情源头针对其他高致病性丝状病毒，如苏丹病毒。
