Experimental Ebola vaccines
Phase 1 clinical trials
WHO and other partners have helped facilitate expedited evaluation of these two vaccines in order to generate phase 1 safety and immunogenicity data for decision-making. A series of coordinated phase 1 trials is currently under way or will soon be initiated with international consortia at more than 10 sites in Africa, Europe and North America.
These studies aim to ensure good communication and harmonization of key design elements to allow for merging of data from different trials of the same candidate products.
The trials, which are being conducted in healthy human volunteers, are designed to test safety and immunogenicity and select the appropriate dose. Two phase 1 trials of the cAd3-ZEBOV started in September 2014 in USA and UK, and the first Phase 1 trial of VSV-ZEBOV is due to start early in October in USA.
The government of Canada has donated 800 vials of rVSV-ZEBOV to WHO. Once data on dosing from phase 1 trials become available, this donation could translate into about 1500 to 2000 doses of vaccine.
Both companies are working to augment their manufacturing capacity. The goal is a very significant increase in scale during the first half of 2015.
One shared mindset was readily apparent during the two-day discussions. Nothing must be allowed to slow down the goal of making vaccines accessible to people in affected West African countries. The phrase, “Nothing can be allowed to delay this work”, was heard over and over again.
The ambition: to accomplish, within a matter of months, work that normally takes from two to four years, without compromising international standards for safety and efficacy.
In other words: to give the African people and their health authorities the best product that the world’s scientists, working collectively, have to offer.
What the experts considered
Against this background, the meeting looked specifically at the objectives and key design elements for moving in an expedited manner to conduct additional clinical trials (phase 2 trial designs) that will generate additional safety data and evidence that the vaccine confers protection.
Parallel pathways for emergency use of experimental candidate vaccines with data collection, among frontline health care workers and other critical personnel, were also explored.
Apart from the great sense of urgency, the overall spirit of the discussions was characterized by a strong sense of solidarity with the people of West Africa, their governments, and their medical, scientific, and public health communities.
Equally strong was the insistence on ensuring that evidence on safety, immunogenicity, and efficacy of the vaccines is collected properly.
Multiple potential challenges and uncertainties were put forward and assessed. Issues ranging from barriers to rapid implementation of R&D, to the design of trials and their use to guide eventual widespread vaccination, were discussed together with proposed ways to overcome them.
Some of the practical issues discussed included how to address communities’ perceptions regarding vaccines in general, and vaccine studies more specifically, public expectations for vaccine availability for widespread use, and whether there is an adequate infrastructure in place to rapidly and safely evaluate and distribute vaccines.
One important technical challenge is the fact that the candidate vaccines must be stored at a temperature of -80°C.
Further issues that need to be urgently addressed include identifying staff who can conduct trials meeting international standards, logistical issues (such as cold chain needs for the vaccines), and the resources needed to start the studies quickly.
Some of the scientific challenges include how to conduct studies as safely and rapidly as possible to inform decisions about mass production of vaccines and their administration.