Background. The 2014 West African outbreak of Ebola virus disease highlighted the urgent need to develop an effective Ebola vaccine. Methods. We undertook 2 phase 1 studies assessing safety and immunogenicity of the viral vector modifed vaccinia Ankara virus vectored Ebola Zaire vaccine (MVA-EBO-Z), manufactured rapidly on a new duck cell line either alone or in a heterologous prime-boost regimen with recombinant chimpanzee adenovirus type 3 vectored Ebola Zaire vaccine (ChAd3-EBO-Z) followed by MVA-EBO-Z. Adult volunteers in the United Kingdom (n = 38) and Senegal (n = 40) were vaccinated and an accelerated 1-week prime-boost regimen was assessed in Senegal. Safety was assessed by active and passive collection of local and systemic adverse events. Results. Te standard and accelerated heterologous prime-boost regimens were well-tolerated and elicited potent cellular and humoral immunogenicity in the United Kingdom and Senegal, but vaccine-induced antibody responses were signifcantly lower in Senegal. Cellular immune responses measured by ffow cytometry were signifcantly greater in African vaccinees receiving ChAd3 and MVA vaccines in the same rather than the contralateral limb. Conclusions. MVA biomanufactured on an immortalized duck cell line shows potential for very large-scale manufacturing with lower cost of goods. Tis frst trial of MVA-EBO-Z in humans encourages further testing in phase 2 studies, with the 1-week primeboost interval regimen appearing to be particularly suitable for outbreak control. Clinical Trials Registration. NCT02451891; NCT02485912.
Bibliographical noteFunding Information:
Financial support. This work was supported by the Wellcome Trust, the UK Medical Research Council, the UK Department for International Development, and the UK NIHR Oxford Biomedical Research Centre. The Good Manufacturing Practice biomanufacture of MVA-EBO-Z and the UK clinical trial was supported by an Enhancement Award to a Wellcome Trust Strategic Award (to A. V. S. H. as principal investigator) co-funded by the Medical Research Council, the Department for International Development, and the European and Developing Countries Clinical Trials Partnership (grant number 106325/Z/14/A), with additional support from the NIHR Oxford Biomedical Research Centre. The Senegal trial was largely funded by a European Commission Horizon 2020 program award EbolaVac (www.ebolavac.eu; grant agreement 666085), which provided additional resources for the MVA-EBO-Z biomanufacture. This study was also supported by GlaxoSmithKline Biologicals SA. Potential conflicts of interest. F. R. and W. R. B. are employees of GSK and own restricted shares of the company. S. C. G., K. E., and A. V. S. H. are named inventors on patents relating to viral vector vaccines for malaria and other diseases. F. R. and W. R. B. are employees of GSK, which is developing vectored vaccines for Ebola and other diseases. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Disclaimer. This paper presents independent research supported by the National Institute for Health Research (NIHR) Clinical Research Facility at Imperial College Healthcare National Health Service (NHS) Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
© 2018 The Author(s).
- Ebola, vaccine
- Viral vectors