Potent immunogenicity and protective efficacy of a multi-pathogen vaccination targeting Ebola, Sudan, Marburg and Lassa viruse.

Autor: Flaxman A; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Sebastian S; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Appelberg S; Public Health Agency of Sweden, Solna, Sweden., Cha KM; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Ulaszewska M; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Purushotham J; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Gilbride C; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Sharpe H; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Spencer AJ; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Bibi S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Wright D; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Schmidt I; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Dowall S; UK Health Security Agency, Porton Down, Salisbury, Wiltshire, United Kingdom., Easterbrook L; UK Health Security Agency, Porton Down, Salisbury, Wiltshire, United Kingdom., Findlay-Wilson S; UK Health Security Agency, Porton Down, Salisbury, Wiltshire, United Kingdom., Gilbert S; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Mirazimi A; Public Health Agency of Sweden, Solna, Sweden., Lambe T; Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom.; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jun 26; Vol. 20 (6), pp. e1012262. Date of Electronic Publication: 2024 Jun 26 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012262
Abstrakt: 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.
Competing Interests: TL reports consulting fees from Vaccitech on an unrelated project, an honorarium from Seqirus, grant support from the DHSC for this work, and is named as an inventor on a patent application for a vaccine against SARS-CoV-2. SG is named as an inventor on patents covering use of ChAdOx1-vectored vaccines and a vaccine against SARS-CoV-2.
(Copyright: © 2024 Flaxman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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