Ebola vaccine trials: progress in vaccine safety and immunogenicity

ABSTRACT

Introduction: Ebolaviruses are non-segmented negative-strand RNA viruses in the Filoviridae family that cause a neglected infectious disease designated as Ebola virus disease (EVD). The most prominent member is the Ebola virus (EBOV), representing the Zaire ebolavirus species that has been responsible for the largest reported EVD outbreaks including the West African epidemic and the current outbreak in the Democratic Republic of the Congo. Today, the most advanced EVD vaccine approaches target EBOV and multiple phase 1–4 human trials have been performed over the past few years. The most advanced platforms include vectored vaccines based on vesicular stomatitis virus (VSV-EBOV), distinct human (Ad5 and Ad26) and chimpanzee (ChAd3) adenoviruses and modified vaccinia Ankara (MVA) as well as DNA-based vaccines administered as a prime-only or homologous or combined prime-boost immunization.

Areas covered: Here, we review and discuss human trials with a focus on vaccine safety and immunogenicity.

Expert opinion: Despite obvious progress and promising success in EBOV vaccine development, many shortcomings and challenges remain to be tackled in the future.

KEYWORDS:

• Ebola virus
• vaccines
• clinical trials
• safety
• immunogenicity
• efficacy

Article highlights

• Ebola virus (EBOV), representing the Zaire ebolavirus species within the family Filoviridae, has been responsible for multiple outbreaks of Ebola virus disease (EVD) since 1976.

• The most advanced filovirus vaccine approaches target EBOV with multiple phase 1–4 human trials using prime-only and prime-boost strategies.

• The most advanced vaccine approaches include the vesicular stomatitis virus (VSV), human (Ad5, Ad26) and chimpanzee (ChAd3) adenovirus, modified vaccinia Ankara (MVA) and DNA platforms as single or combined strategies.

• Human trials assigned the above-mentioned vaccine approaches in general a good safety profile.

• Human trials demonstrated good immunogenicity for the above-mentioned vaccine approaches but correlates and mechanisms of protection are not defined.

• Europe, Russia and China have licensed EBOV vaccine products thus far.

Acknowledgments

The authors are grateful to Ryan Kissinger (Visual and Medical Arts, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)) for his help with the graphical illustrations.

Declaration of interest

H Feldmann claims intellectual property regarding vesicular stomatitis virus-based filovirus vaccine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Peer Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Disclaimer

The opinions, conclusions, and recommendations in this report are those of the authors and do not necessarily represent the official positions of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH).

Additional information

Funding

Work on filoviruses by the authors is supported by the Intramural Research Program of the NIAID, NIH.