A study published in Science demonstrates that vaccination with a mutated form of the Ebola virus provides some measure of protection to non-human primates. This finding places the vaccine one step closer to clinical trials in humans.

The researchers publishing this study have developed what’s called a “whole virus” vaccine for Ebola. Viruses have proteins on their exterior and genetic material on their interior. Whole virus vaccines present the host’s immune system with multiple viral proteins and the viral genetic material. These vaccines trigger broader immune system responses than vaccines that only present a single protein from the virus. Whole virus vaccines have had widespread success in offering protection against potentially deadly diseases such as smallpox, measles, and influenza.

But, in order for these vaccines to be safe and effective, the virus has to be weakened. The new vaccine relies on a strain of Ebola called EBOVDVP30, which has a key gene deleted. It provides some protection against Ebola in studies that used mice and guinea pigs.

In the new study, the researchers actually tested three ways of weakening the virus. In one test, they inoculated macaque monkeys with the vaccine either once or twice, and then exposed them to a lethal dose of the Ebola virus. A second group of macaques was immunized once or twice with a hydrogen peroxide treated version of the vaccine prior to their viral exposure, to examine the effects of this treatment on vaccine effectiveness. A third group of macaques that were inoculated with a gamma-irradiated version of the Ebola virus was also included, to assess the utility of that exposure in terms of developing immunity. A control group of macaques were not vaccinated before being exposed to the same lethal dose of the virus.

The investigators found that all macaques that were vaccinated either once or twice with the EBOVDVP30 vaccine or the hydrogen peroxide treated vaccine survived their infection with the virus. This was in stark contrast to the control group, all of which were euthanized according to humane endpoint criteria, which specifies that animal subjects that are critically ill and will not recover must be humanely euthanized. The macaques that were treated with the irradiated Ebola virus were also all humanely euthanized according to the same endpoint criteria, suggesting this method of exposure to the virus did not provide protection.

The two groups of macaques that were euthanized showed high levels of the Ebola virus in their blood after their exposure. In contrast, there was no detectable Ebola virus in the blood of macaques that were immunized either once or twice, regardless of whether their vaccine was treated with hydrogen peroxide.

A lone exception was one animal that had been treated with a single inoculation of the untreated vaccine, yet showed evidence of viral infection three days after exposure. But that animal successfully cleared the virus by the ninth day after exposure. Another one of the animals that was vaccinated once showed signs of a fever after exposure, but also recovered. This finding is important because it indicates that the vaccine may not wholly prevent Ebola virus replication in the host’s system, and may not protect from all symptoms of the virus. Critically, however, it will protect the host from death attributable to the virus.

An examination of the immune response measured in tissues from animals involved in this study indicated that the EBOVDVP30 vaccine generated an antibody response that was important for protection against the Ebola virus.

When Ebola was first discovered, there were efforts to develop a whole virus vaccine for the virus, but those vaccines failed to produce complete protection in non-human primates. At that time, attempts to generate a whole virus vaccine for Ebola were largely abandoned in favor of vaccines that focused on viral proteins. The vaccine investigated in this paper could provide an alternate strategy for Ebola protection.

Science, 2015. DOI: 10.1126/science.aaa4919 (About DOIs).