First Ebola virus vaccine to protect human beings?

www.thelancet.com Published online December 22, 2016 http://dx.doi.org/10.1016/S0140-6736(16)32618-6 1 Since the discovery of Ebola virus in 1976, researchers have attempted to develop eff ective vaccines. Early eff orts were largely stalled as a result of the small global market for a vaccine for Ebola virus disease because of an absence of fi nancial incentives for pharmaceutical companies. After the attacks in the USA on Sept 11, 2001, several governments invested in Ebola virus because they had concerns that it could be used as a biological weapon. These investments laid the groundwork for several candidate vaccines for Ebola virus disease that showed promise in preclinical studies in animals. Among the most promising vaccines showing protection in the gold standard non-human primate models of Ebola virus disease was a vaccine based on a recombinant vesicular stomatitis virus expressing the Ebola virus glycoprotein (rVSV-ZEBOV). Findings from preclinical studies in non-human primates jointly fi nanced by the Public Health Agency of Canada and the US Defense Threat Reduction Agency showed that the rVSV-ZEBOV vaccine could completely protect non-human primates as a preventive vaccine against all medically relevant species of Ebola virus when given as a single-injection vaccine; protect 50% of non-human primates against Ebola virus disease when given shortly after exposure; and seemed to be safe in non-human primates as evidenced by an absence of serious adverse events in severely immunocompromised animals and no evidence of neurovirulence in non-human primates. Outbreaks of Ebola virus disease have occurred sporadically, mostly in central Africa since 1976. These outbreaks have been small in size and generally well contained until December, 2013, when the largest recorded outbreak of Ebola virus disease began in the west African country of Guinea and quickly spread to surrounding countries with cases also being exported to Europe and the USA. As the outbreak grew in magnitude and appeared to be uncontained, eff orts to use medical counter-measures to intervene intensifi ed. In an Article published in The Lancet, Ana Maria Henao-Restrepo and colleagues follow-up their interim results and present the fi nal results of their ring vaccination cluster-randomised trial in Guinea in 2015 to assess the effi cacy of a single intramuscular dose of the rVSV-ZEBOV vaccine in the prevention of laboratory confi rmed Ebola virus disease. The study involved vaccinating a ring of all contacts and contacts of contacts of confi rmed cases of Ebola virus disease, either immediately or delayed to 21 days after randomisation. Briefl y, 2119 contacts and contacts of contacts in 51 clusters randomly allocated, and 1677 contacts and contacts of contacts in 19 non-randomised clusters were immediately vaccinated, and 2041 contacts and contacts of contacts in 47 randomised clusters received a delayed vaccination 21 days after randomisation. Importantly, no cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters compared with 16 cases in those in delayed clusters. Vaccine effi cacy was 100% (95% CI 68·9–100·0, p=0·0045). Vaccine effi cacy was also 100% in the non-randomised clusters (95% CI 79·3–100·0, p=0·0033). These data strongly suggest that the rVSV-ZEBOV vaccine was eff ective in protecting against Ebola virus infection and probably contributed to controlling the 2013–16 outbreak of Ebola virus disease in Guinea. Protective effi cacy is clearly the strength of the study by Henao-Restrepo and colleagues. There have been concerns in the past regarding the safety profi le of rVSV-ZEBOV because it is a replicationcompetent vaccine. In this study, the investigators identifi ed 80 serious adverse events, of which only two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly First Ebola virus vaccine to protect human beings?