Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial
2015
Summary Background
Ebola virusand Marburg virus cause serious disease outbreaks with high
case fatality rates. We aimed to assess the safety and immunogenicity of two investigational
DNA vaccines, one (EBO
vaccine) encoding
Ebola virusZaire and Sudan
glycoproteinsand one (MAR) encoding Marburg virus
glycoprotein. Methods RV 247 was a phase 1b, double-blinded, randomised, placebo-controlled clinical trial in Kampala, Uganda to examine the safety and immunogenicity of the EBO and MAR
vaccinesgiven individually and concomitantly. Healthy adult volunteers aged 18–50 years were randomly assigned (5:1) to receive three injections of
vaccineor placebo at weeks 0, 4, and 8, with
vaccineallocations divided equally between three active
vaccinegroups: EBO
vaccineonly, MAR
vaccineonly, and both
vaccines. The primary study objective was to investigate the safety and tolerability of the
vaccines, as assessed by local and systemic
reactogenicityand adverse events. We also assessed immunogenicity on the basis of antibody responses (ELISA) and T-cell responses (ELISpot and intracellular cytokine staining assays) 4 weeks after the third injection. Participants and investigators were masked to group assignment. Analysis was based on the intention-to-treat principle. This trial is registered at ClinicalTrials.gov, number NCT00997607. Findings 108 participants were enrolled into the study between Nov 2, 2009, and April 15, 2010. All 108 participants received at least one study injection (including 100 who completed the injection schedule) and were included in safety and tolerability analyses; 107 for whom data were available were included in the immunogenicity analyses. Study injections were well tolerated, with no significant differences in local or systemic reactions between groups. The
vaccineselicited antibody and T-cell responses specific to the
glycoproteinsreceived and we detected no differences between the separate and concomitant use of the two
vaccines. 17 of 30 (57%, 95% CI 37–75) participants in the EBO
vaccinegroup had an antibody response to the Ebola Zaire
glycoprotein, as did 14 of 30 (47%, 28–66) in the group that received both
vaccines. 15 of 30 (50%, 31–69) participants in the EBO
vaccinegroup had an antibody response to the Ebola Sudan
glycoprotein, as did 15 of 30 (50%, 31–69) in the group that received both
vaccines. Nine of 29 (31%, 15–51) participants in the MAR
vaccinegroups had an antibody response to the Marburg
glycoprotein, as did seven of 30 (23%, 10–42) in the group that received both
vaccines. 19 of 30 (63%, 44–80) participants in the EBO
vaccinegroup had a T-cell response to the Ebola Zaire
glycoprotein, as did 10 of 30 (33%, 17–53) in the group that received both
vaccines. 13 of 30 (43%, 25–63) participants in the EBO
vaccinegroup had a T-cell response to the Ebola Sudan
glycoprotein, as did 10 of 30 (33%, 17–53) in the group that received both
vaccines. 15 of 29 (52%, 33–71) participants in the MAR
vaccinegroup had a T-cell response to the Marburg
glycoprotein, as did 13 of 30 (43%, 25–63) in the group that received both
vaccines. Interpretation This study is the first Ebola or Marburg
vaccine trialdone in Africa, and the results show that, given separately or together, both
vaccineswere well tolerated and elicited antigen-specific humoral and cellular immune responses. These findings have contributed to the accelerated development of more potent
Ebola virus
vaccinesthat encode the same wild-type
glycoproteinantigens as the EBO
vaccine, which are being assessed during the 2014
Ebola virusdisease outbreak in west Africa. Funding US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program.
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