A monovalent chimpanzee adenovirus ebola vaccine boosted with MVA

K. Ewer, T. Rampling, N. Venkatraman, G. Bowyer, D. Wright, T. Lambe, E. B. Imoukhuede, R. Payne, S. K. Fehling, T. Strecker, N. Biedenkopf, V. Krähling, C. M. Tully, N. J. Edwards, E. M. Bentley, D. Samuel, G. Labbé, J. Jin, M. Gibani, A. MinhinnickM. Wilkie, I. Poulton, N. Lella, R. Roberts, F. Hartnell, C. Bliss, K. Sierra-Davidson, J. Powlson, E. Berrie, R. Tedder, F. Roman, I. De Ryck, A. Nicosia, N. J. Sullivan, D. A. Stanley, O. T. Mbaya, J. E. Ledgerwood, R. M. Schwartz, L. Siani, S. Colloca, A. Folgori, S. Di Marco, R. Cortese, E. Wright, S. Becker, B. S. Graham, R. A. Koup, M. M. Levine, A. Volkmann, P. Chaplin, A. J. Pollard, S. J. Draper, W. R. Ballou, A. Lawrie, S. C. Gilbert, A. V.S. Hill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

228 Citations (Scopus)

Abstract

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-1×1010 viral particles, 2.5×1010 viral particles, and 5×1010 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 two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone.

Original languageEnglish
Pages (from-to)1635-1646
Number of pages12
JournalNew England Journal of Medicine
Volume374
Issue number17
DOIs
Publication statusPublished - 28 Apr 2016
Externally publishedYes

Bibliographical note

Funding Information:
Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.

Publisher Copyright:
Copyright © 2016 Massachusetts Medical Society. All rights reserved.

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