Update on Ebola vaccine: report on phase 1 trials
In the wake of the Ebola virus outbreak being declared a public health emergency of international concern by the World Health Organization (WHO), the vesicular stomatitis virus Ebola Consortium (VEBCON) was established (under auspices of WHO) in August 2014. Here the aim was to initiate phase 1 testing of the replication-competent recombinant vesicular stomatitis virus (rVSV)–vectored Zaire ebolavirus (rVSV-ZEBOV) candidate vaccine. The Canadian Government donated a total of 800 vaccine doses to the WHO. Preclinical safety records demonstrated that among approximately 80 immunized non-human primates, none displayed detectable toxic effects. In addition, none of the animals exhibited detectable illness after immunization. For phase 1, three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial were performed to determine the safety, side-effect profile, and immunogenicity of the rVSV-ZEBOV vaccine. This was done at various doses for a period of six months in healthy adults in Europe and Africa (Lambaréné, Gabon; Kilifi, Kenya; Hamburg, Germany; and Geneva, Switzerland). This study showed that while the vaccine was reactogenic, no serious adverse effects were reported. More importantly, the vaccine was immunogenic with all participants producing sustained levels of anti-bodies throughout the 180 days. Greater antibody titers were observed at higher concentrations of the vaccine. The authors report that this vaccine resulted in a favourable risk– benefit balance and that the data from phase 1 contributed to the dose selection process performed by the vaccine manufacturers. It has raised the awareness about the specific adverse events to be expected with the use of the rVSV-ZEBOV vaccine to all stake-holders. In addition, it has resulted in the introduction of safety-driven changes in the protocols for the ongoing phase 2 and 3 studies.
Kareemah Gamieldien (PhD, Physiology)
Cape Peninsula University of Technology
S.T. Agnandji, A. Huttner, M.E. Zinser, et al. 2016. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med, 374;17: 1647-1660.