Ebola vaccines: an uncertain future?
Authors: Zoë Mullan
Journal: The Lancet Global Health (2015)

On Jan 28, the preliminary phase 1 safety data for GlaxoSmithKline's (GSK's) candidate Ebola vaccine were published. The chimpanzee adenovirus vector (ChAd3) vaccine, which encodes a wild-type surface glycoprotein from Zaire Ebolavirus, raised no safety concerns in the 60 healthy volunteers from the UK tested and showed reasonable immunogenicity. Five days later, the first dose was given to a Liberian man as part of an expedited phase 3 trial in west Africa. Phase 1 trials of at least two other candidates are in progress: Merck's Zaire-strain-encoding vesicular stomatitis virus (VSV) vector, and Johnson & Johnson's heterologous prime-boost vaccine based on human Ad26 and modified vaccinia Ankara (MVA) vectors expressing Zaire strain glycoprotein. The rapid roll-out of these trials has been tremendously impressive. Yet none of the vaccines were originally developed with African public health in mind: they were created out of fear that the virus could be used as a bioweapon. Concerns over limited market size and recipient governments’ ability to pay meant that the business case for a population-level Ebola vaccine was flimsy. Now, as the epidemic wanes and phase 3 trials and licensing become more complex, there is a risk that manufacturers will revert back to this previous state of thinking. Declining case numbers have already led drug manufacturer Chimerix to pull out of a trial of brincidofovir in Liberia. This is disheartening to say the least. The reduction in incidence of Ebola virus disease has been brought about by means of a combination of scaled-up treatment capacity, safe burial practices, and rigorous case and contact finding. Vital communication and consultation work with communities has improved trust and understanding. But, as Brian McCloskey from the Office of the UN Special Envoy on Ebola was at pains to point out at a seminar in London last week, the outbreak cannot yet be considered under control. In fact a slight uptick in cases since the beginning of February illustrates his point. He further emphasised that the outlook is now not one of a single epidemic across three countries, but of perhaps 60 or more localised outbreaks with the very real potential to spread across borders into countries such as Mali and Côte d'Ivoire. The UN's response strategy is now moving away from a concentration on treating the vast volume of cases and towards elimination of transmission. Here vaccines play a vital role. It was ring vaccination—ie, the vaccination of a “ring” of individuals potentially exposed to a case—that saw the eradication of smallpox in 1980. Furthermore, as Peter Piot noted at the same seminar, Ebola's ability to disrupt the whole health system by means of decimating the workforce is as potent a threat as its case–fatality rate. Vaccination of health workers could neutralise this threat. With the UN's focus now on case and contact finding and with a still-uncertain epidemic trajectory, the drive to bring vaccines (and the more the better) to licensing and production should not falter. So what of the realities of this for vaccine manufacturers? There is hope. First, a willingness to collaborate between governments, funding bodies, and companies has been key to the success of the vaccine trials so far. The phase 1 GSK vaccine trial in the UK, for example, was funded by the Wellcome Trust, the UK Department for International Development, the UK Medical Research Council, and the UK National Institute for Health Research. Financial support for its further development is being provided by the European Union, the Bill & Melinda Gates Foundation, and the Swiss Government. GSK has committed to scaling up vaccine production even as later-phase trials are ongoing. Second, governments are offering levers such as tax incentives and extended exclusivity rights to drive manufacturers on. And third, regulators are showing signs of flexibility in terms of accelerated licensure in the event that the waning epidemic delays the ability to demonstrate efficacy. Vaccines are not a magic bullet. Nothing can replace the basic tenets of public health epidemiology and community mobilisation. But in the early days of a new outbreak in an unprepared population, as in all likelihood will happen again, vaccines can be a vital early weapon. Once we are reasonably assured of safety and efficacy, everything must be done to ensure that stockpiles are ready and the necessary clearances for their use are in place. For the GSK phase I trial results see N Engl J Med 2015; published online January 28. http://www.nejm.org/doi/full/10.1056/NEJMoa1411627#t=article For the GSK phase I trial results see N Engl J Med 2015; published online January 28. http://www.nejm.org/doi/full/10.1056/NEJMoa1411627#t=article For more on Chimerix's exit from brincidofovir trials see http://www.msf.org.uk/article/liberia-ebola-drug-trial-halted For more on Chimerix's exit from brincidofovir trials see http://www.msf.org.uk/article/liberia-ebola-drug-trial-halted For the latest WHO Ebola situation report see http://apps.who.int/ebola/ For the latest WHO Ebola situation report see http://apps.who.int/ebola/