An experimental vaccine against Ebola virus seems to be safe and commands a strong immune response against the virus, according to tests in 20 healthy people in the United States. The results of the phase 1 trial are published in the New England Journal of Medicine.
“All in all, I would say it was a successful phase 1 study,” says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, which co-developed the drug with the London-based drug company GlaxoSmithKline (GSK). “The next steps are to move ahead with a larger efficacy trial in West Africa.”
The vaccine is similar to one that is on track to be tested in larger trials in West Africa, which are likely begin early next year. In these phase 2 and phase 3 trials, thousands of people who are at risk of contracting the virus, such as health workers, will receive the vaccine to determine whether it can protect against infection.
The vaccine that has been tested in the United States was made from a cold-causing chimpanzee adenovirus that had been engineered to express proteins from two species of the Ebola virus, known as Zaire and Sudan (after their origins), and that was already available when the trial began in early September. However, the outbreak in West Africa is caused by a strain of virus from the Zaire species, known as Zaire-Guinea. Vaccine developers have agreed that so-called monovalent vaccines that target only the Zaire species should be deployed in West Africa. Safety tests of one such vaccine, also developed by GSK and the NIAID, began in October at several sites, including in Switzerland, the United Kingdom and Mali.
In the trial of the bivalent vaccine, volunteers received one of two doses. None of the participants developed any major health problems, though two ran a brief fever within a day of getting the higher dose. Blood samples from all the participants contained antibodies against at least one of the species or strains. But volunteers who received the high dose of the vaccine made more antibodies against the Zaire-Guinea strain than did those who received a lower dose.
Only an efficacy trial involving people at risk of infection can reveal whether a vaccine prevents infection. But the levels of antibodies that the high-dose volunteers generated were in line with those seen in monkeys that were protected from Ebola after receiving the same vaccine, Fauci says.
“The immune responses are there, the tough call is whether they’re enough to protect humans against Ebola, and I guess we’ll find that out in the phase 3 trial,” says Adrian Hill, director of the Jenner Institute in Oxford, UK, who is leading a small safety trial of the monovalent NIAID/GSK vaccine. “The big caveat here is this is not the vaccine that will be used in West Africa.”
Daniel Bausch, a physician at Tulane University in New Orleans, Louisiana, who wrote an editorial accompanying the paper, says that the immune responses look good, but are difficult to interpret. Researchers do not know what kind of immune response is necessary to prevent an Ebola infection, he says. “Since we don’t know where the bar is, that’s a challenge in interpreting these kinds of studies.”
Other Ebola vaccines are also being fast-tracked for clinical trials. The Public Health Agency of Canada has developed a vaccine made from a virus related to rabies and licensed it to NewLink Genetics in Ames, Iowa, and to Merck in Whitehouse Station, New Jersey. Safety tests have already begun. Meanwhile, phase 1 trials are to begin early next year for a two-vaccine regimen involving an adenovirus-based vaccine developed by US pharmaceutical company Johnson & Johnson and the NIAID, and a vaccine that is made from vaccinia (a virus similar to the one that causes cowpox) developed by Bavarian Nordic in Denmark.
“It’s really impressive that we have these data in such a short time span,” says Hill. “This trial was started in September and here we’re looking at a paper in November.”
This article is reproduced with permission and was first published on November 27, 2014.