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Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus

2015; Nature Portfolio; Volume: 520; Issue: 7549 Linguagem: Inglês

10.1038/nature14428

1476-4687

Chad E. Mire, Demetrius Matassov, Joan B. Geisbert, Theresa Latham, Krystle N. Agans, Rong Xu, Ayuko Ota‐Setlik, Michael A. Egan, Karla A. Fenton, David K. Clarke, John H. Eldridge, Thomas W. Geisbert,

Hepatitis B Virus Studies

Two second-generation attenuated Ebola virus vaccines based on recombinant vesicular stomatitis virus protect macaques against infection with a recent Ebola virus isolate from Guinea. The N1 and N4 rVSV vectors described in this manuscript are the subject of patents licensed to Profectus BioSciences, Inc. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the University of Texas Medical Branch. Two variants of the recently developed VesiculoVax recombinant vesicular stomatitis virus (VSV)-based Ebola vaccine have been tested for their ability to protect cynomolgus monkeys against heterologous challenge with the new outbreak strain of Ebola virus. Animals received a single injection of either N4CT1 or N1CT1 VesiculoVax and were exposed to a high dose of Ebola four weeks later. None of the vaccinated animals developed illness and all survived. This works raises the prospect that second-generation vaccines may have fewer safety concerns than the first-generation vaccines currently in use in the field. The family Filoviridae contains three genera, Ebolavirus (EBOV), Marburg virus, and Cuevavirus1. Some members of the EBOV genus, including Zaire ebolavirus (ZEBOV), can cause lethal haemorrhagic fever in humans. During 2014 an unprecedented ZEBOV outbreak occurred in West Africa and is still ongoing, resulting in over 10,000 deaths, and causing global concern of uncontrolled disease. To meet this challenge a rapid-acting vaccine is needed. Many vaccine approaches have shown promise in being able to protect nonhuman primates against ZEBOV2. In response to the current ZEBOV outbreak several of these vaccines have been fast tracked for human use. However, it is not known whether any of these vaccines can provide protection against the new outbreak Makona strain of ZEBOV. One of these approaches is a first-generation recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing the ZEBOV glycoprotein (GP) (rVSV/ZEBOV). To address safety concerns associated with this vector, we developed two candidate, further-attenuated rVSV/ZEBOV vaccines. Both attenuated vaccines produced an approximately tenfold lower vaccine-associated viraemia compared to the first-generation vaccine and both provided complete, single-dose protection of macaques from lethal challenge with the Makona outbreak strain of ZEBOV.