What’s in the needle? A look at Ebola vaccine candidate VSV-EBOV

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Transmission Electron Microscope image of Vesicular Stomatitis Virus (source: Wikipedia)

[B]eginning about fifteen years ago, several teams of researchers in various nations began in earnest to pursue a viable vaccine against Ebola and Marburg filoviruses. In about 2013, two candidates reached monkey experiments (what are commonly called ‘non-human primate’ trials) and reported rousing success. Today, we’ll discuss one of those candidates, VSV-EBOV.

Yesterday, news percolated throughout the MSM that VSV-EBOV would be the first filovirus vaccine to be tried on humans in the United States (currently, a human trial is being conducted in West Africa on health worker volunteers, but more on that tomorrow). According to an article from CBC.ca:

The first human clinical trials of a Canadian-developed Ebola vaccine, VSV-EBOV, begin in Maryland today to assess the vaccine’s safety and determine the appropriate dosage to fight the virus that has killed more than 4,000 people, largely in West Africa, Health Minister Rona Ambrose has announced.

“We are able to share some very promising and hopeful news in the fight against Ebola,” Ambrose said from Calgary.

[…]The vaccine, which was developed by scientists at the Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg, will be tested on 20 healthy volunteers at the Walter Reed Army Institute of Research in Silver Spring, Md.[i]

So, what’s in the vaccine? To begin with, VSV-EBOV is a type of recombinant vector vaccine. This technology is relatively new, and simply means that the genome of the ‘vector’ has been altered. Vectors are like molecular trucks, and in this case the ‘truck’ is VSV.

The VSV in the working name (I’m sure it will be given a memorable, brand name once it’s through the trial chain) stands for ‘Vesicular Stomatitis Virus’, sometimes called ‘Vesicular Stomatitis Indiana Virus’ (I just had to make sure my home state is included). VSV is a member of the Family Rhabdoviridae, and her more sinister sister in that family is commonly called rabies. Viruses in this family are vector-borne, meaning that in real life, they rely on an insect or other ‘biter’ to inject the viral payload.

So, how will it be used to protect against Ebola? Both Ebola and VSV use trickery to gain entry into human cells: they wear a human cell outer membrane envelope, like wearing the uniform of the ‘good guys’. Sticking out of this ‘friendly’ membrane are proteins called ‘Glycoproteins’ (GPs), which carry specific sugar residues that allow this protein to ‘shake hands’ with receptor proteins on human cells. This initiates a process called ‘endocytosis’. If the cell is a ‘home’, then the owner has just opened the door and brought the dangerous but friendly looking package inside. Once inside the cell, the virus sheds its outer membrane allowing the RNA inside to begin using the transcription and assembly capability of the host cell to replicate its evil payload. These newly assembled genomes and accompanying viral proteins then travel to the cell wall where they ‘bud off’ (wrap themselves in the host cell membrane) and travel to the next cell. This process is quite similar to the way Ebola virus invades host cells, except Ebola destroys the host cell, while VSV generally does not. VSV does demonstrate an affinity for destroying cancer cells, which is why it has been used in cancer and HIV therapeutics.

In VSV-EBOV, the wildtype (unaltered) vesicular stomatitis virus has been genetically altered so that its outer glycoproteins are Ebola GPs. In theory, this teaches the human body’s immune system to recognize the Ebola glycoprotein as an invader. So far, the new vaccine candidate has been used on Ebola-challenged crab-eating monkeys, but very few humans have been tested until now. There are reports that indicate neurological side-effects from recombinant VSV (in a study using crab-eating monkeys, two of three monkeys developed observable neurological defects, apparently caused by spinal cord lesions).[ii] This shouldn’t be a major surprise, because wildtype VSV is known to cause neurological problems in non-humans and occasionally in humans.[iii]

Here’s another point to consider: Current clinical trials in humans will probably be lauded as successful if challenged subjects do not become ill. But what about long-term follow-up? Neurological side-effects may not emerge for weeks to months—perhaps even years. Viruses are tricky, and they love to nestle into our tissues and wait for opportune moments to pop up and say hello. Anyone who has ever suffered from Shingles can attest to this truth.

Don’t misunderstand my caution: I would love to see Ebola forever eliminated from the planet, but that probably isn’t going to happen—at least, not today. Would I take an Ebola vaccine? No. Not unless someone forces me to do so. For now, in America, we still have free will. For now.

 

Endnotes:

[i] http://www.cbc.ca/news/world/ebola-outbreak-1st-human-trials-of-canadian-vaccine-start-in-u-s-1.2796859

[ii] http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001567

[iii] http://bvs1.panaftosa.org.br/local/file/textoc/Allende-vesicular-stomatitis2003.pdf