| Authors | Ewer, K., Rampling, T., Venkatraman, N., Bowyer, G., Wright, D, Lambe, T., Imoukhuede, E.B., Payne, R., Fehling, S.K., Strecker, T., Biedenkopf, N., Krähling, V., Tully, C.M., Edwards, N.J., Bentley, E.M., Samuel, D., Labbé, G., Jin, J., Gibani, M., Minhinnick, A., Wilkie, M., Poulton, I., Lella, N., Roberts, R., Hartnell, F., Bliss, C., Sierra-Davidson, K., Powlson, J., Berrie, E., Tedder, R., Roman, F., De Ryck, I., Nicosia, A., Sullivan, N.J., Stanley, D.A., Mbaya, O.T., Ledgerwood, J.E., Schwartz, R.M., Siani, L., Colloca, S., Folgori, A., Di Marco, S., Cortese, R., Wright, E., Becker, S., Graham, B.S., Koup, R.A., Levine, M.M., Volkmann, A., Chaplin, P., Pollard, A.J., Draper, S.J., Ballou, W.R., Lawrie, A., Gilbert, S.C. and Hill, A.V.S. |
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| 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 glyco- protein, 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 (geo- metric 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. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.) |
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