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Everything You Need To Know About An Ebola Vaccine

Vaccines are the best way to stop the Ebola epidemic. Here’s how they work and what you need to know about the two experimental ones that are furthest along.

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Ebola has been winning this from the start. Since the outbreak began in March, the grim reality of the virus’s march through West Africa and beyond has been laid out in a growing string of data points, the graph showing the number of cases swooping upward in that telltale pattern of exponential growth. The outbreak broke 10,000 cases right around the time the World Health Organization warned of a future with 10,000 cases a week. This isn’t just a fight; this is a war. Which is why, if we are going to beat Ebola, we are going to need an army.

But not the 4,000 troops President Obama recently made available to be sent to countries ravaged by the epidemic. To outsmart the virus, we must raise an army to fight Ebola where it counts the most: inside the body.

Treatment saves those already infected, but vaccines stop the spread of the virus. Treat Ebola and you may save the patient, but not before the virus has ample opportunity to jump to a caretaker or neighbor or someone else. The only way to end the war is to stop infections from happening in the first place.

Period.

There are at least two promising vaccines in the pipeline. These vaccines will need to train the elegant and maddeningly complicated defense systems of the human body to find and destroy Ebola virons before they can get a hold inside the body.

Your body, in all of its warm, wet, and dark wonder, makes a great home for many organisms looking to get out of the cold, bright, dry world around them. Life arose from the ocean, and we carry a reminder of that precious, ancient home inside our skin as we move about through our desiccant world on land; naturally, we’re an appealing place to try to break into.

This isn’t always terrible. We form alliances with many microorganisms — such as the beneficial gut microbes we rely on for digestion. But not all guests are so well behaved. Some of them act like squatters who occasionally deface property; others slip in and set fire to everything in their sights. And your immune system must be able to remember the faces of all the inimical intruders.

Determining friend or foe sounds deceptively simple until you consider not only the diversity of cell types and tissues in the human body, but also the multitude of bacteria, fungi, and viruses a body must successfully identify and chose whether or not to fight. Which would explain how the immune system came to be a sprawling and highly coordinated biochemical military-industrial conglomerate, second only to the nervous system in terms of complexity.

And, perhaps even more incredibly, with inoculations we learned that we could send our immune systems pages of biological cables with detailed instructions on training troops to meet the threats yet unseen. Ladies and gentlemen, meet your own private infantry.

Your defenses break down into two categories: innate and acquired. Innate immunity is the stuff you’re born with, such as skin, mucus for trapping things, stomach acid to ward off food poisoning, and a cough reflex to eject those that would enjoy the kush digs of your delicate lungs. (Your innate immunity also includes types of white blood cells that attack certain very common invaders.)

On the other hand, acquired immunity is built and trained from scratch. How does it learn? From exposure to antigens, a catchall term for anything that can provoke an immune response, be it biological or not, including things such as pieces of viruses and bacteria, toxins, drugs, even a splinter in your finger. Over the course of your lifetime, your acquired immune system will learn to recognize millions of threats and develop ways to deal with all of them.

That your acquired immune system can only fight what it has been specifically trained to recognize honestly sounds fucking insane: The cells and proteins tasked with protecting your fragile meat sack have to learn to fight each new invader. From the ground up. This is how it happens.

Say you’re chewing your nail on the bus. It’s probably fine because most of the crap under your fingernails is stuff you’ve encountered before. But maybe today, you decide to go in for some cuticle, nibbling off just enough skin to create a shallow, irritating wound on the side of your finger, laying out a welcome mat for the bacteria ever hopeful for a trip inside. The breach in your flesh-based hazmat suit sounds an alarm, calling all manner of soldiers to the location to begin the process of defense and repair, furiously working amid a cacophony of chemical signalling to destroy the foreign invaders. There’s a problem, and the immune system is on it. (One only needs to look how quickly bacteria riot through the body after death to get a sense of just how busy the immune system is, 24/7.)

This isn’t to imply that the relationship between you and your immune system is a friendly one, however. In fact, the tenuous peace between the two of you is known as “self-tolerance.” Given the opportunity, your immune system will happily and swiftly turn on you, as anyone with an autoimmune disorder can attest. In fact, the only reason your immune system isn’t carpet bombing you right now is because the outside of your cells have proteins on them that the patrolling troops recognize as part of the same team: self, not other.

When the infantry arrives at the site of the wound, they get right to work, identifying non-self materials and looking for familiar antigens. For all the antigens you’ve encountered, your body keeps a few copies of the cells, called B cells, that can recognize them; when one of these cells sees an old foe, it slaps an antibody on it like a condemned sign, sealing its fate and marking it for destruction. It also initiates a process to ramp up a full army of other cells that can fight that one antigen.

But say there’s something new in your cut. Something that slips by the initial defenses, a bacteria or virus that your immune system has never before encountered. Your immune system will send specialized cells to find and eat these strangers, breaking them down and shoving the foreign antigens onto their own cell surfaces like big, neon “kill me” signs. This sends out the call to killer T cells, which find the marked cells and destroy them.

Meanwhile, helper T cells show up and start sending dispatches near and far, calling B cells to the area to ramp up antibody production, as well as more killer T cells and cells equipped to deal with the wreckage and subsequent garbage disposal.

However, there is one downside to this elegant solution: You have to get the disease and win the battle before your body will have the information it needs to beat it again. That’s no problem with the common cold. But it’s a big problem with Ebola, which is currently killing half of its victims.

With vaccines, however, we’ve figured out how to train our immunological militias to fight dangers yet unseen. A jab with a needle and we can load in a warning that says, “This is the enemy. Learn to fight it. Remain vigilant.” And in the race to halt the epidemic burning through West Africa, vaccine researchers are working to present Ebola’s dirty T-shirt to the bloodhounds patrolling your streams. One good whiff and they’ll recognize Ebola the way sharks always know when there’s blood in the water.

Traditionally, vaccines have been made one of two ways: killed or weakened. A killed virus, like Jonas Salk’s polio vaccine, teaches the immune system to fight by using the corpses of dead viruses. A weakened, or “attenuated,” virus does the same, but with a version of the virus that is unable to infect the host. The former is a punching bag, the latter a gentle sparring partner.

The Ebola vaccines currently being tested are a newer breed, relying on cut-and-paste molecular biology to clip precise snippets of Ebola genetic material and plunk them into an entirely different — and harmless — virus. It’s the immunological equivalent of a lamb in wolf’s clothing, teaching the body to fight Ebola by creating a safe version that looks like the real thing.

The first vaccine is GlaxoSmithKline’s cAd3-EBO Z, which rolled out its phase one clinical trial last month. (A phase one trial doesn’t try to determine if the vaccine works. Rather, it tests whether the vaccine is safe and whether it provokes a robust immune response.) This vaccine is being developed in collaboration with the U.S. National Institute of Allergy and Infectious Diseases (NIAID).

The second, which healthy volunteers began testing this month in a phase one trial, is rVSV-ZEBOV. Developed by Public Health Agency of Canada, it’s been licensed by the American company NewLink Genetics.

How these vaccines are built reads like bizarro science fiction. The Glaxo vaccine pops a little segment of harmless Ebola code into a virus that gives chimpanzees the sniffles, while its Canadian cousin sews a stretch of Ebola’s genetic material into a virus that makes cows break out in skin ulcers.

For simplicity’s sake, I’m going to call them Chimp Sniffles and Cow Blister, respectively.

Cow Blister (rVSV-ZEBOV) started out as a vesicular stomatitis virus, VSV. A member of the Rhabdoviridae family – which also includes rabies and the lesser-known lettuce necrotic yellows virus – this virus infects livestock: cattle, horses, pigs.

When animals get sick with VSV, they look like Seabiscuit with nightmare herpes, their lips and cheeks blooming with fluid-filled mucosal vesicles and raw ulcerations. Infections in humans are very rare and have been reported in cases of direct exposure such as a lab accident and contact with infected animals; thankfully, in people it is also much less aesthetically confrontational, resulting in a mild flu-like illness, if symptoms even bother to show up at all.

One of the proteins encoded in VSV’s genome is its envelope, a sheath that covers all the other proteins of the virus. VSV’s envelope is what allows the virus to break into the cell by mimicking the secret biochemical handshake of a more welcome protein. And, lucky for us, it turns out that the VSV envelope is also what causes disease.

What happens from here is your basic Mr. Potato Head. Researchers chunk out the envelope gene from their Cow Blister virus, which simultaneously weakens it and removes the virus’s genetic blueprints for causing harm. The warm spot left by the now-gone VSV envelope gene is then reclaimed by that of an Ebola envelope gene. The technical term for such swappery is recombination. Cow Blister is a live, attenuated recombinant, vesicular stomatitis virus-cum-vaccine vector, which is a really precise way of saying it’s something harmless dressed up in an Ebola costume. Teach the guards to recognize the costume so when the real deal shows up, everybody already knows who they are, preventing the Ebola virus from slipping under the immunogenic radar, as is its modus operandi. And no: You cannot get Ebola from this vaccine any more than you can fill your stomach with the aroma of food cooking.

GSK’s “Chimp Sniffles” (cAd3-EBO Z) does the same thing with a different virus, an chimp adenovirus, which causes the common cold in our primate cousins. Originally, researchers were super hot for adenoviruses as a potential vectors for gene therapy. Today, they have been comprehensively studied, so researchers are able to precisely customize these viruses — with minimal surprises.

The Chimp Sniffles vaccine was built to trick the immune system into thinking it is fighting Ebola by splicing benign bits of it into the chimpanzee-derived adenovirus — a cold virus. This recombination of genetic material is the same cut-and-paste as in the previously discussed vaccine — the envelope of the adenovirus is removed and replaced by the Ebola envelope. When this amalgamated virus is introduced to the body, it hops right on existing cellular machinery and starts pumping out the harmless Ebola protein it’s been designed to express.

Once the body notices the Ebola envelope protein, it starts churning out specialized patrol guards, training them to recognize the new and hostile contortions of amino acids. That way, if a person ever meets the real Ebola virus, their immune system will be ready to fight it off.

So far, the vaccine has only been tested in humans to see if it’s safe, not if it works. But in monkeys, both vaccines have been shown to protect the animals from an injection of Ebola.

Moreover, the Cow Blister vaccine has also shown promise in monkeys as a treatment after they had already contracted Ebola.

However, according documents obtained by ScienceInsider from an Oct. 23 meeting at the World Health Organization, even the best case scenario for vaccine deployment in the field is months away. Currently, Glaxo’s vaccine is the furthest along in development; the preliminary data from its phase 1 trial should be ready for analysis by November. If the results are promising, efficacy trials could begin in January. Glaxo also outlined how production could be scaled up during the trial period, so that the vaccine could be ready for wider distribution by April 2015. That is an extremely fast track for a vaccine — the process usually takes years — and it assumes that all goes perfectly with the trials.

This is Ebola. Learn to fight it. Remain vigilant.


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Leigh Cowart is a freelance journalist. Her work has appeared in Hazlitt, The Independent, Vice, Deadspin, and others. She was once vaccinated for rabies and has been drunk with power ever since. [leigh.cowart@gmail.com]

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