A vaccine from a neutralized virus
Three mutations in the ebolavirus genome allowed macaques to be vaccinated
Polina Loseva, N+1
American scientists were able to make Javanese macaques resistant to Ebola. To do this, they introduced mutations into the genome of the virus that prevented it from blocking the immune response of animals. After vaccination with the neutralized virus, the monkeys steadfastly endured the introduction of a lethal dose of the usual virus. Despite the fact that it is too early to talk about the use of a new vaccine in humans, the virus can already be used in laboratories without endangering experimenters. The study is published in the journal Cell (Woolsey et al., A VP35 Mutant Ebola Virus Lacks Virulence but Can Elicit Protective Immunity to Wild-Type Virus Challenge).
Ebola outbreaks still occur every now and then in Africa. There is no reliable cure for it yet, vaccines remain the main way to prevent the epidemic. However, those vaccines that are currently in development immunize a person with only one antigen – the surface protein of the viral capsid. At the same time, immune cells specific to a variety of viral proteins can be found in patients who have had a fever. This means that vaccination against ebolavirus can also be made more effective by targeting the immune system at several targets at once.
To achieve this result, it is necessary to introduce a weakened, but "live" virus into the human body, on the surface of which there will be many different proteins at once. Similar viruses have already been used to practice vaccination on mice and guinea pigs. However, in order to infect these animals, which are usually resistant to ebolavirus, it had to be changed quite a lot. To vaccinate people, you will still need the original ebolavirus.
Courtney Woolsey and her colleagues from the University of Texas Medical Department worked with Javanese macaques, they are also crab-eating macaques. These animals suffer from the Ebola virus in the same way as humans, and die of fever after a week of illness.
To neutralize the virus, scientists have introduced several mutations into its genome. All of them affected one gene – VP35. It encodes the VP35 protein, which prevents the host's immunity from detecting the virus in time. Many cells have sensory molecules that react to the appearance of a double–stranded RNA molecule - a sure sign of viral infection. VP35 prevents sensors from contacting RNA and suppresses their activity, thereby making the virus elusive in the early stages of infection. When the immune system detects the virus, its spread can no longer be stopped.
The researchers found that three mutations in VP35 allow cells to respond to a viral infection in time and start producing antiviral interferon proteins. At the same time, defects in VP35 do not prevent the virus from multiplying.
Scientists injected this weakened virus into three macaques to test whether it worked as a vaccine. A month after the first injection, the animals were infected with the usual Ebola virus. Two of the three macaques survived, the third died – but only on day 9, which is 3 days later than the average time of death of monkeys from this infection.
Then five more animals received ten times the dose of the vaccine. It was necessary to find out if it has a dose-dependent effect. When, a month later, these macaques were injected with a lethal dose of the virus, all five underwent the injection well, they developed only mild side effects. One of the animals died, but the authors of the work attribute this to the neurological problems of the monkey itself, and not to the consequences of infection.
Following this, scientists confirmed that the new version of the virus really works like a vaccine: genes associated with activation and recognition of the antigen are triggered in the cells of the immune system, that is, the body reacts to the weakened virus as an enemy and develops an immune response.
It is not yet necessary to say that a weakened virus can serve as a vaccine for humans. It has yet to be studied in detail for side effects and to choose a safe dose. Nevertheless, the researchers believe that it can already be used for laboratory experiments and not assign them the highest level of biological hazard.
Other unforeseen difficulties also stand in the way of fighting Ebola: for example, patients who have had an infection continue to die more often than other people even after being discharged from the hospital.
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