From bench to almost bedside: the long road to a licensed Ebola virus vaccine

ABSTRACT

Introduction: The Ebola virus (EBOV) disease epidemic during 2014–16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques.

Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans.

Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics.

KEYWORDS:

• Clinical trials
• ebola virus
• nonhuman primates
• vaccines

Declaration of Interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Article highlights

• An abundance of vaccine candidates have performed well with pre-clinical testing in NHPs.

• Some candidates have hurdles to overcome before advancement to clinical trials due to safety reasons (RABV and EBOVΔVP30, and at one point live, replicating recombinant viruses such as VSV).

• Phase 1 trials have demonstrated the safety and immunogenicity of Ad5-EBOV, ChAd3-EBO Z, and VSVΔG/EBOVGP vaccines.

• Clinical trials to evaluate the efficacy of ChAd3-EBO Z, VSVΔG/EBOVGP, and the Ad26.ZEBOV and MVA-BN-Filo heterologous prime-boost regimen were initiated in affected areas of West Africa, most were unable to elucidate efficacy due to the decline of the epidemic by late 2015.

• Only VSVΔG/EBOVGP has demonstrated preliminary efficacy in a clinical trial setting, demonstrating 100% efficacy by the end of 2015.

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Additional information

Funding

This work is supported by the National Key Research and Development Program of China (2016YFE0205800), the National Key Program for Infectious Disease of China (2016ZX10004222), the Sanming Project of Medicine in Shenzhen (ZDSYS201504301534057), the Shenzhen Science and Technology Research and Development Project (JCYJ20160427151920801), and the Public Health Agency of Canada, partially supported by grants from the National Institutes of Health (U19AI109762-1 to GP Kobinger and X Qiu), Canadian Institutes of Health Research (IER-143487 to X Qiu), and National Natural Science Foundation of China International Cooperation and Exchange Program (8161101193 to G Wong). The authors declare no conflict of interest.