While there was a decline in new cases of Ebola in December and January in the three West African countries most affected by the virus (Liberia, Guinea and Sierra Leone), this trend seems to have ended. Ebola transmission was widespread in Guinea and Sierra Leone in February, but remained low in Liberia, according to the World Health Organization (WHO Ebola Situation Report, 25 Feb 2015, http://apps.who.int/ebola/en/ebola-situation-report/situation-reports/ebola-situation-report-25-february-2015 ). Unfortunately, a significant portion of new cases do not have a known cause of transmission. The race for a vaccine has also heated up, with 6 vaccines now in clinical development, both single vaccines and multiple vaccine regimens.
Of the 6 vaccines in clinical development for preventing Ebola infection, 2 vaccines are in Phase III and 4 vaccines are in Phase I (Figure 1). The most advanced vaccines are New Link Genetics’ vesicular stomatitis vaccine (rVSV-EBOV) in collaboration with Merck, and Okairos’ (GSK’s) adenovirus vaccine (cAd3-EBO-Z), which are both currently being studied in the 28,000+ subject PREVAIL trial in Liberia. Primary outcome data from this trial is due to be collected in June 2015.
Okairos (GSK) has 2 vaccines in the clinic (Figure 2) in different stages: their monovalent (Zaire strain only) cAd3-EBOZ vaccine in Phase III and a bivalent form of the vaccine in Phase I, which contains both Sudan and Zaire Ebola strains and is based on the same adenoviral vector. Their monovalent cAd3-EBO-Z vaccine is also being studied in a Phase I clinical trial as a priming vaccine with Bavarian Nordic’s MVA-BN Filo vaccine as the boost vaccine in a prime-boost regimen.
Of the 4 vaccines in Phase I, 2 are being developed by Johnson & Johnson and Bavarian Nordic for use together in a prime-boost strategy. This regimen uses Johnson & Johnson’s adenovirus-based prime vaccine (Ad26.ZEBOV) with Bavarian Nordic’s MVA-BN Filo boost vaccine. As mentioned previously, the MVA-BN Filo vaccine is also being investigated as a boost vaccine to Okairos’ (GSK’s) cAd3-EBO-Z vaccine in a Phase I trial. The final Phase I vaccine is being developed by Novavax (EBOV-GP), and uses their nanoparticle vaccine technology with their Matrix-M adjuvant.
Given the high mortality of Ebola and the recent increase in Ebola transmission, development of a vaccine to combat this virus is as urgent as ever. Ebola has appeared in 6 additional countries to date via travel from a country with widespread transmission; Mali, Nigeria, Senegal, Spain, the UK and the US. This highlights the potential spread of the epidemic and the need for effective treatments and vaccines for this deadly virus. 2015 is anticipated to be a very active year for Ebola vaccine development and clinical trials.