Adenovirus-vectored Ebola vaccines

Abstract

The 2014 outbreak of Ebola virus disease in West Africa has highlighted the need for the availability of effective vaccines against outbreak pathogens that are suitable for use in frontline workers who risk their own health in the course of caring for those with the disease, and also for members of the community in the affected area. Along with effective contact tracing and quarantine, use of a vaccine as soon as an outbreak is identified could greatly facilitate rapid control and prevent the outbreak from spreading. This review describes the progress that has been made in producing and testing adenovirus-based Ebola vaccines in both pre-clinical and clinical studies, and considers the likely future use of these vaccines.

Keywords:

• clinical trials
• Ebola virus disease
• outbreak pathogen
• replication-deficient adenoviral vector
• response to vaccination
• simian adenoviral vector
• vaccination

Financial & competing interests disclosure

Sarah Gilbert is a named inventor on patent filings related to immunization with vectored vaccines, specifically WO2008/122769. The author has 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.

Key issues

• Replication-deficient, adenoviral vectored vaccines expressing the glycoprotein of Ebola virus induce strong humoral and cellular responses.

• The use of rare human serotypes or simian adenoviruses avoids pre-existing immunity to adenovirus serotype 5 in humans.

• In non-human primates, a single dose of adenovirus serotype 5 or chimpanzee adenovirus 3-vectored vaccines provided complete protection against high dose challenge. Post-exposure prophylaxis has also been demonstrated.

• The vaccines can be manufactured at a large scale and were found to be safe and well tolerated in clinical trials, with a very low rate of post-vaccination fevers. IgG and cellular immune responses were both induced within 14 days, and could be boosted to higher levels by a single dose of MVA expressing Ebola virus glycoprotein.

• Currently available data indicate that systemic side effects of vaccination are considerably lower after vaccination with an adenovirus-vectored vaccine compared to a vesicular stomatitis virus-vectored vaccine. Direct comparison of immunogenicity is not possible with currently available data, but this should change in the near future.