A New Ebola Vaccine Is Related To Rabies. Is It Safe?

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An experimental vaccine offers total protection against Ebola, according to preliminary results from a large clinical trial.

Among 4,000 vaccinated people, there were no cases of infection. The study concluded that the vaccine – known as ‘rVSV-ZEBOV’ – is “highly efficacious and safe in preventing Ebola virus disease”. Here’s all you need to know about the new vaccine.

What is rVSV-ZEBOV?

The vaccine contains a live virus: Vesicular Stomatitis Virus, or VSV.

It’s closely related to Rabies. Both are members of the Rhabdoviridae family, with bullet-shaped virus particles that infect mammal cells. But unlike Rabies, which has a case fatality rate of almost 100% if left untreated, VSV infection is far from deadly.

“It usually leads to very mild disease,” says Dr Heinz Feldmann, chief of virology at the US National Institute of Allergy and Infectious Diseases, who designed the rVSV-ZEBOV vaccine.

The virus was tamed in the late 1990s by molecular virologist John Rose, who created an ‘attenuated’ virus – a genetically-engineered version with a lower virulence than the natural pathogen. Feldmann then replaced a VSV gene with one from Ebola.

VSV’s genetic code has instructions for producing 5 proteins, while Ebola’s genome encodes 7. Both have virus particles covered with one type of protein on the surface, which attaches to a host cell and allows the parasite to invade.

Feldmann swapped the gene for the VSV surface protein with the one from Ebola, creating a ‘recombinant’ virus – one with a new combination of genes. The protein comes from the Zaire species of Ebola, hence ‘rVSV-ZEBOV’.

How does it work?

Vaccination trains the body to develop immunity to specific proteins – antigens. If a foreign pathogen replicates inside a host cell, the proteins it releases are detected by white blood cells (mainly B-cells), which learn to recognize those antigens. The immune system then adapts by producing matching antibodies that help neutralize or destroy the invaders.

Ebola victims can make antibodies against the virus naturally, but that adaptive immune response can take several days – too late to beat an infection, as the virus normally kills in the second week after exposure.

The vaccine prompts immune cells to make antibodies against the antigens produced by the genetically-modified VSV – including the Ebola protein.

“The immune response immediately recognizes that outer surface protein of Ebola because it had seen it before through the vaccine,” Feldmann explains. “The immune response kicks-in very, very quickly, and can then eliminate or at least limit the infection to an extent that the person can survive.”

Is the vaccine safe?

Yes. But as with many medicines, some patients will experience side effects.

Although rVSV-ZEBOV uses an Ebola protein to invade cells, all its other proteins come from Vesicular Stomatitis Virus, which causes mild disease.

The alternative is to risk suffering from Ebola, a virus that invades blood cells and vessels, causing severe hemorrhagic fever. It’s extremely virulent and kills up to 90% of susceptible individuals.

Ebola is a BioSafety Level 4 pathogen and requires maximum containment, whereas VSV is merely level 1. Heinz Feldmann originally developed rVSV-ZEBOV to study how the Ebola virus invades cells under less dangerous and less restrictive lab conditions.

Working with immunologist Thomas Geisbert, he tested the vaccine on rodents and non-human primates. In a 2005 study in Nature Medicine, they showed that a single injection protected monkeys against lethal doses of Ebola, and that no animals developed fever or other symptoms of illness.

Feldman says it’s a very powerful vaccine. “We only need one shot.”

Developed while he was a researcher at the Public Health Agency of Canada, rVSV-ZEBOV was licensed to NewLink Genetics and then Merck, which manufactures a high-quality, clinical-grade vaccine. In early 2015, it passed Phase 1 and 2 clinical trials, which mainly test for safety in human subjects.

How effective is rVSV-ZEBOV?

Effectiveness is tested at Phase 3, which is usually a large-scale study required for regulatory approval.

The Phase 3 trial was carried out in Guinea and employed the approach used to eradicate Smallpox, a containment strategy for infectious diseases called ‘ring vaccination’. After a person is infected, their circle of contacts is identified and vaccinated in the hope of stopping an outbreak from spreading.

The study involved two groups of people: one where adults who had been in contact with an Ebola patient were vaccinated immediately, and another group where people received the vaccine 3 weeks later. (There was no control group where subjects received a placebo because it would be unethical to withhold a potential treatment – those tests occurred in the earlier phases.)

From a population of 7,651 individuals, 4,123 were randomly assigned to the immediate vaccination group, in which there were no cases of Ebola after 10 days, the incubation time of the virus. In the delayed vaccination group, there were 16 cases.

The vaccine therefore provides 100% protection when given as a prophylactic treatment. While drugs such as ZMapp have gained media attention, rVSV-ZEBOV is the first vaccine to be proven effective.

Another live virus has also been engineered to carry Ebola genes: chimpanzee adenovirus type 3, or ChAd3-ZEBOV. The virus, which causes colds in chimps, was developed by the National Institute of Allergy and Infectious Diseases and pharmaceutical firm GSK. ChAd3-ZEBOV has also reached Phase 3 trials.

Vaccines that contain viruses that don’t replicate in host cells are generally considered safer than live viruses, but they’re also less potent.

“We knew that there was a trade-off,” says Feldmann. “But we thought for an emergency situation, this might be a compromise.”

JV Chamary is a biologist and writer – read his stories on Forbes and follow him on Google+ and Twitter

Source: Forbes