PDF(Pubmed)
Abstract：
Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.
摘要：
病毒性出血热（VHF）对人类健康构成重大威胁。近年来,由埃博拉病毒引起的VHF爆发，马尔堡病毒和拉萨病毒在西非和中非造成了大量的发病率和死亡率。2022年，由苏丹病毒引起的乌干达埃博拉疫情导致164例病例，55例死亡。2023年，在赤道几内亚和坦桑尼亚确认了马尔堡病爆发，导致超过49例确诊或疑似病例；其中41例是致命的。对这些VHF的防护没有明确的关联，阻碍靶向疫苗的发展。因此,所开发的任何疫苗应诱导针对这些病毒的强的和优选持久的体液和细胞免疫。理想情况下，这种免疫力也应该交叉保护免受病毒变异，已知在动物水库中循环并引起人类疾病。我们利用了两个病毒载体疫苗平台,腺病毒（ChAdOx1）和改良的安卡拉痘苗（MVA），开发针对三种丝状病毒(埃博拉病毒，苏丹病毒,马尔堡病毒）和沙粒病毒（拉沙病毒）。这些平台技术一直证明了在人类中诱导强大的细胞和体液抗原特异性免疫的能力。最近推出了许可的ChAdOx1-nCoV19/AZD1222。这里,我们证明我们的多病原体疫苗能引起强大的细胞和体液免疫，诱导不同范围的趋化因子和细胞因子，最重要的是,在致命的埃博拉病毒之后提供保护，苏丹病毒和马尔堡病毒在小动物模型中的挑战。
