Vaccination Research · 2016 · pp. 1–6 · e-ISSN 2771-750X

Leading Ebola Vaccine Candidates

Vincent PAVOT

DOI: https://doi.org/10.17140/vroj-1-101 · Published 2016-02-17 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2016 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

Abstract

The ongoing outbreak of Ebola Virus Disease (EVD) in West Africa is the largest outbreak ever recorded with a total number of 28,602 confirmed, probable, or suspected cases in Guinea, Liberia, and Sierra Leone, including 11,301 reported deaths since December 2013 (as of January 17, 2016).1 A meeting convened by the World Health Organization (WHO) in September, 2014, concluded that an urgent unmet need exists for efficacy and safety testing of the EVD vaccine candidates and that clinical trials should be expedited. These vaccines could be used both in an outbreak setting and to provide long-term protection in populations at risk of sporadic outbreaks. A number of vaccines have been evaluated in phase 1 trials including DNA vaccines, virus-like particles and viral vectors,2 but the two most advanced first-generation Ebola vaccines candidates are the live replicating Vesicular Stomatitis Virus (rVSV) and the replicationdefective chimpanzee adenovirus 3 (ChAd3).

Conclusion

The recent Ebola epidemic has galvanized the development of filovirus vaccines and presented a unique set of challenges that required extraordinary collaboration, flexibility, and innovation among a number of entities with a broad range of expertise to secure global health. These entities included government agencies, especially health officials from the affected West African countries, non-governmental organizations, academic research groups, pharmaceutical companies, and the WHO. This lead to an unprecedented speed of Ebola vaccine testing since late 2014 with multiple candidates in advanced stages of clinical development.

Current efforts to develop a vaccine are focused on the viral GP encoded by the virus. The most advanced first-gener ation Ebola vaccines candidates tested so far are the live repli cating rVSV-ZEBOV and the replication-defective ChAd3-ZE- Page 5 BOV based on the GP from the Zaire strain of Ebola virus. Trials being undertaken in Africa, Europe and US have already shown that these vaccines are safe and well-tolerated and, although a human correlate of protection remains unknown, a single dose of rVSV-ZEBOV or ChAd3-ZEBOV is able to generate putatively protective Ab titers. ChAd3 vaccine on its own especially at 1011 should be effective as it produces Ab titers at least as high as VSV and greater cellular immunity (which is relevant at least in NHPs).

These immune responses are significantly enhanced in prime-boost regimes using MV A-based virus vectors as a boosting vaccination, although the optimal interval between the priming and boosting vaccination has not yet been determined. Although the promising efficacy of rVSV vaccine is encouraging, challenges remain in improving vaccines to provide durable efficacy and identifying optimal ways for vaccine deployment. Moreover, as a general rule, live-replicating viruses such as VSV-vectored vaccines are contraindicated in people with an immunodeficiency (e.g. HIV +) and children, since the vaccine strain could be pathogenic, particularly when non-replicating viral vectors such as adenoviruses have shown good safety in those two groups. Clinical assessment should continue to allow a full comparison of ChAd3 alone, ChAd3/MV A, Ad26/ MV A and rVSV for safety, with particular emphasis on the rate of post-vaccination fevers and arthritis, and for immunogenic ity, preferably in African populations where the vaccine will be needed in future.

Some 300,000 doses of rVSV-ZEBOV vaccine against EVD will be available from May 2016 for use in emergency situations and clinical trials, under a deal signed by the drug company Merck and by Gavi, a vaccine provider to the poorest countries in the world.

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