A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA

作者：Katie Ewer, Tommy Rampling, Navin Venkatraman, Georgina Bowyer, Danny Wright, Teresa Lambe, Egeruan Babatunde Imoukhuede, Ruth Payne, Sarah Katharina Fehling, Thomas Strecker, Nadine Biedenkopf, Verena Krähling, Claire Maria Tully, Nick J. Edwards, Emma M. Bentley, Dhanraj Samuel, Geneviève M. Labbé, Jing Jin, Malick M. Gibani, Alice Minhinnick, Morven Wilkie, Ian D. Poulton, Natalie Lella, Rachel M. Roberts, Felicity Hartnell, Carly M. Bliss, Kailan Sierra-Davidson, Jonathan Powlson, Eleanor Berrie, Richard S. Tedder, François P. Roman, Iris De Ryck, Alfredo Nicosia, Nancy J. Sullivan, Daphne A. Stanley, Olivier Tshiani Mbaya, Julie E. Ledgerwood, Richard M. Schwartz, Loredana Siani, Stefano Colloca, Antonella Folgori, Stefania Di Marco, Riccardo Cortese, Edward Wright, Stephan Becker, Barney S. Graham, Richard A. Koup, Myron M. Levine, Ariane Volkmann, Paul Chaplin, Andrew John Pollard, Simon J. Draper, W. Ripley Ballou, Alison M. Lawrie, Sarah C. Gilbert, Adrian V. S. Hill · 发表于：New England Journal of Medicine · 年份：2015 · DOI：10.1056/nejmoa1411627 · 被引用次数：357 · 研究领域：Viral Infections and Outbreaks Research、SARS-CoV-2 and COVID-19 Research、Vaccine Coverage and Hesitancy

BACKGROUND: The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS: In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels--1×10(10) viral particles, 2.5×10(10) viral particles, and 5×10(10) viral particles--with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime-boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS: No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the t...