Squirting a vaccine up the nostrils of a camel is not the easiest thing in the world to do, Bart Haagmans has discovered. “They are difficult characters,” as he put it. “Sometimes they are a bit grumpy.”
But the effort was worth it for the Dutch virologist. Haagmans and an international team of colleagues reported Thursday in the journal Science that their experimental MERS vaccine worked.
The vaccine didn’t completely block dromedary camels from becoming infected with the coronavirus that causes MERS, short for Middle East respiratory syndrome. But it substantially reduced the amount of MERS viruses the camels spewed out while infected, a fact the scientists believe would, in turn, substantially lower the risk of camels infecting people with the virus.
“If we’re going to stop the transmission of MERS virus in hospitals, we’ve got to stop it from getting to humans in the first instance. And the only way we’re going to do that is break that interface between the camel and the human,” said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy. Osterholm was not involved in the research.
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The MERS virus is a cousin of the one that caused SARS, which triggered an explosive global outbreak in 2003. The previously unknown virus infected more than 8,400 people in roughly 30 countries, killing 916 of the infected. It took just under four months from the time the World Health Organization warned there was a new disease spreading until the time it declared the outbreak over.
MERS, on the other hand, has been a slow-motion outbreak. First spotted in June 2012, it has infected just over 1,600 people in 26 countries since then and killed at least 584. Occasional primary cases — people thought to be infected by camels — occur. The bulk of infections, though, arise in hospitals, when unrecognized MERS patients aren’t isolated. Hospital outbreaks can involve dozens or scores of cases.
Most of the cases have occurred on the Arabian Peninsula, though South Korea experienced a big outbreak — 186 cases, 36 deaths — when a businessman returned there after becoming infected while traveling in the Middle East.
SARS was contained when authorities in China ordered that the animals that had transmitted the virus to people — civet cats — be removed from the country’s so-called wet markets, where live animals are sold to be butchered for food. But camels are active — even treasured — parts of daily life in some Middle Eastern and African countries. They are raced, used as beasts of burden, slaughtered for food, milked, even kept as pets.
More outbreaks like the ones that devastated hospitals in South Korea will crop up unless a way to stop camel-to-human transmission is devised. Infectious diseases experts talk about turning off the tap or “pulling the pump handle” — a reference to legendary epidemiologist John Snow, who famously inactivated a communal water pump in central London in 1854, thereby proving that contaminated water was the cause of recurrent cholera outbreaks, not bad air as was the prevailing view at the time.
“To me this is the easiest and most logical way to pull the pump handle,” Osterholm said of the work to develop a MERS vaccine for camels.
The need appears to be significant. A second study, published with Haagmans’s, reported on the results of a surveillance program undertaken of camels in Saudi Arabia, which has had the vast majority of MERS cases. From May 2014 to April 2015, researchers tested 1,309 camels at slaughter houses, on farms and in markets; 12 percent were infected with the MERS coronavirus at the time they were tested.
The vaccine study is only a proof of principle, cautioned Haagmans, a virologist from the Erasmus Medical Center in Rotterdam; more work will be needed. His group gave two doses of the vaccine to four camels and gave placebos to four more. Three weeks later, all the animals had big doses of MERS virus puffed up their nostrils to see if the vaccinated animals were protected. One of the vaccinated camels did not get as much protection as the three others; the researchers don’t know why.
The vaccine’s design is clever, chosen both to maximize the chances that it would work and that it would be an attractive option for camel owners, who may someday be asked to incur the cost of vaccinating their animals to protect people.
Research done after the SARS outbreak showed at least one experimental vaccine that used the whole coronavirus actually made vaccinated mice sicker when they were exposed to the virus. So Haagmans felt designing a vaccine that used the whole MERS virus wasn’t an option.
Instead, he and his colleagues genetically engineered another virus to produce a key MERS protein. The virus they used is called MVA, short for modified vaccinia Ankara; it’s a poxvirus, a highly weakened relative of the smallpox virus. It’s often used in vaccine development as a way of introducing part of a pathogen — in this case the MERS spike protein — to the immune system to provoke antibody production.
The beauty of using MVA is that it also gives camels protection against a related virus called camelpox. That would make this a two-for-one vaccine, protecting camels against a disease that is for them severe while lowering the risk they will infect people with the MERS virus.
That’s important because a MERS vaccine on its own would be unlikely to be a priority for camel owners. The virus triggers only mild symptoms in dromedaries; it’s the equivalent of a human case of the sniffles.
Haagmans said in theory the same design could be used for a MERS vaccine for people. But the economics of a human MERS vaccine are questionable.
Developing, testing, and gaining regulatory approval for a human vaccine would take years and hundreds of millions of dollars. Some work on a human vaccine is underway and early-phase clinical trials are expected to start in the new year. But as long as MERS remains a disease afflicting small numbers of people, pharmaceutical companies are unlikely to proceed very far with this type of project.
By comparison, making an animal vaccine is less expensive and the regulatory hurdles that such a product would face could be lower, Osterholm said.
Dr. Marie-Paule Kieny, a WHO executive who leads an effort to develop vaccines and drugs for diseases like Ebola and MERS, said she thinks the camel vaccine is worth pursuing.
Kieny noted questions were raised about the economic viability of a vaccine for Hendra virus, a bat virus that can infect horses which can then infect people. Hendra outbreaks are rare and have only ever been reported in eastern Australia.
The Australian government has promoted the use of Hendra vaccine in horses, helping to create a market, Kieny said. She said if the governments of MERS-affected countries would tell camel owners they should vaccinate their animals, “this would open a market for industry to develop a product.”
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this is interesting