Why a MERS Vaccine Won't Be Easy

Economics and timing complicate vaccine research.

Two years ago, the virus didn't even have a name. A year ago it had infected roughly 50 people, half of whom died. Now, Middle East Respiratory Syndrome has been confirmed in more than 600 people, and killed nearly 30 percent of its victims.

Originating on the Arabian Peninsula, MERS has been carried via travelers to the United States (two reported cases), North Africa, and Malaysia, as well as a handful of European countries.

Adding urgency to the anxiety, the annual pilgrimage to Mecca in early October will draw more than a million people through the city of Jeddah, the outbreak's "ground zero."

Graphic map of how a disease spreads.

With other dangerous diseases, like smallpox, polio, and measles, vaccines provide protection and stop transmission. So why can't we just vaccinate people against MERS and wipe the disease out before it spreads further?

Although the science of making a vaccine against MERS is feasible—unlike, say, HIV, which has stymied researchers for decades—neither the market economy nor the vaccine development process is likely to support it, experts say.

Finding an attackable target on the surface of a virus is relatively easy these days, and there's nothing about the MERS virus that is likely to make it difficult to attack. But testing the safety and effectiveness of a vaccine could easily take six years—as it did to develop a meningococcus B vaccine to address an epidemic in New Zealand—and will likely cost upward of half a billion dollars, said Philip Dormitzer, global head of virology for Novartis Vaccines.

"It's really more of a question now whether developing a human vaccine is the best approach to contain this disease or not, and where one would prioritize that among the multiple vaccine developments that are under way," he said.

Drawbacks to Vaccines

Just over a decade ago, a company called Chiron, since bought by Novartis, started developing a vaccine for Severe Acute Respiratory Syndrome (SARS), which, like MERS, is a member of the coronavirus family. A vaccine candidate showed effectiveness in animals, Dormitzer said, but before it could be tested in people, the disease was contained.

The fact that their effort never led to a commercially successful product could dampen corporate enthusiasm for a MERS vaccine now, he said.

"You certainly can't ignore that precedent," he said, adding that companies have to ask themselves, "Is the disease going to be around by the time we're done with the process?"

Several academic researchers agreed that it doesn't make sense to spend time and money developing a MERS vaccine right now. Despite its recent spread, the disease, first identified in 2012, has been relatively contained so far and doesn't seem to be as contagious as SARS. Also, like any medication, a vaccine would certainly have side effects.

"If we were to vaccinate the entire population of the world, the probability that someone is going to have an adverse reaction to the vaccine is going to be higher than that someone will develop MERS," said W. Ian Lipkin, John Snow Professor and Director of the Center for Infection and Immunity at Columbia University's Mailman School of Public Health.

A highly contagious disease, like the flu, which affects millions and also has the potential to kill, is a more appropriate candidate for a vaccine, said Robert W. Finberg, professor and chairman of the Department of Medicine at the University of Massachusetts Medical School in Worcester.

Avian flu, for instance, worries Finberg much more than MERS does, because it has already infected birds worldwide and millions of people interact with wild birds and poultry every day. Though it hasn't spread much among people yet, if avian flu does transform to become more contagious, it will be hard to stop.

"Bird flu's not going away," said Finberg, who studies flu evolution to predict future strains. "There are too many reservoirs."

Racing Against the Clock

The dismissive talk about a vaccine for people would change completely, though, if MERS becomes more contagious.

Right now, the virus is relatively hard to pass on. One Illinois man caught it during a 40-minute business meeting with a man who'd recently worked in a Saudi hospital. But riding in the same bus or airplane, for instance, isn't believed to be a problem, according to the U.S. Centers for Disease Control and Prevention, which is carefully tracking all the people who came into contact with both men, hoping for insights into the virus's transmissibility.

Viruses evolve quickly, and once they gain a foothold in people, they are more likely to become more contagious. Viruses that are both deadly and readily contagious are every infectious disease expert's worst nightmare. Smallpox was the prime example, and is the one disease that has been eradicated from the Earth—thanks to Edward Jenner, the British doctor who first made the connection between mild cases of cowpox in milkmaids and their subsequent protection against smallpox.

That's why this fall's hajj pilgrimage is such a concern. Having more than a million people in close contact right at the epicenter of the epidemic could become problematic. (See "Q&A: Will MERS Become a Pandemic?")

Researchers like Wayne A. Marasco, an immunologist at Harvard Medical School and the Dana-Farber Cancer Institute, are racing against the clock to find ways to address MERS if it does become more dangerous. Marasco has discovered an antibody that may be able to block or treat the MERS virus.

All viruses have distinctive proteins on their surface. Our white blood cells detect those alien proteins, then make targeted antibodies to hunt them down. If researchers can identify those same proteins on the surface of the virus, they can give the immune system a boost to fight off the disease.

A vaccine triggers white blood cells to make antibodies against those proteins, effectively helping a well person ward off the disease. A monoclonal antibody drug can be designed to track down and kill microbes with those proteins, to fight the virus in someone who is already sick.

Fifteen years, Marasco began collecting vials of antibodies in his Boston lab. He took the genes from these antibodies—each has two—sorted them and recombined them to create new antibodies. The library now has 27 billion pairs of genes.

When MERS was first identified, Marasco did a search of his library and found seven variants of surface proteins in the MERS virus. One seems to be particularly potent, he said, but for human testing, several antibodies would be combined to ensure that if the virus mutated, the vaccine produced would have a "durable life," he said. Tomorrow, he's headed to Qatar to present his MERS antibody work at a conference.

Focus on the Camels

Everyone agrees that the best hope is to stop MERS before it spreads further, the way SARS was stopped by killing the animals that were passing it on.

Camels are our best hope, Lipkin said. Instead of vaccinating people against MERS, the focus should shift to vaccinating camels, which appear to be a crucial point of transmission. "If you eliminate camels as a reservoir, I think you'd have a reasonable shot of getting this under control," he said.

Developing a vaccine for camels would be cheaper, faster, and easier than developing one for people, he said, without the same level of safety concerns. He thinks it's possible to get a vaccine into camels even before October's hajj pilgrimage.

"There are efforts to develop a vaccine under way," Lipkin said. To test such vaccines, researchers must find camels that have not been infected, vaccinate them, expose them to the disease, and then observe them for protection against infection. It's complicated, but much faster and easier than making sure people are helped more than harmed.

Novartis's Dormitzer agrees that the idea has merit. "It's a very interesting thought," he said. "There's a logic to it."

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