Three Kinds of Vaccines Protect Monkeys from Zika

A rhesus macaque monkey in Puerto RicoBrennan Linsley / AP

“What’s the timeline been on the development of these Zika vaccines?” I asked Nelson Michael, a colonel in the U.S. Army Medical Corps and the director of the HIV research program at the Walter Reed Army Institute of Research. He's been working on them since February, and now has published a new paper, with colleagues, reporting that their vaccines were successful in rhesus macaque monkeys.

“Now don’t laugh,” he said. “Let’s go back to 1893.”

That’s when Walter Reed was founded, albeit under a different name. Walter Reed—the person—studied yellow fever, “which is a flavivirus, much like Zika,” Michael says. Reed helped prove that yellow fever is spread by the Aedes aegypti mosquito, as is Zika.

“We always think of flaviviruses at our institute,” Michael said. So when the Zika outbreak ramped up early this year, Michael and his friend Stephen Thomas, a flavivirus expert at Walter Reed, started to work on developing a vaccine.

They created what’s called a whole-kill vaccine, or a purified inactivated virus vaccine. That’s when you take a living virus, kill it with formaldehyde, remove the formaldehyde, and then inject the dead virus into an animal to get an immune response.

Little did Michael and Thomas know that their friend Dan Barouch at Harvard Medical School was also working on a vaccine at the same time—a DNA vaccine, which uses the genetic material that produces the envelope around the virus to spur an immune response.

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One day in March, Barouch called Michael to ask if they perhaps were working on a Zika vaccine, because he wanted to test more than one kind.

“I said, ‘Are you kidding me?’” Michael says.

So they worked together, and in June, they published results in Nature that their vaccines had worked in mice. And in the new study, published in Science on Thursday, both the whole-kill and the DNA vaccines “provided complete protection” to vaccinated monkeys, the study reads, as did a third kind of vaccine in which you “take a harmless virus and you basically make it a bus by sticking in genes from a pathogen,” Michael says. The unvaccinated monkeys showed traces of the virus in their blood, urine, cerebrospinal fluid, cervical fluid, and rectal fluid up to a week after exposure.

“We showed that the vaccines work in mice—okay, well, they're mice.” Michael says. “Some people conceive of mice as cat food. But the fact that they work in nonhuman primates will really wake the field up, because typically that means, whoa, we’re very close now to potentially work in humans.”

The group plans to start clinical trials in humans in October, on the whole-kill vaccine. There will be four trials—three in the U.S. and one in Puerto Rico. Two will be done by the National Institutes of Health, one by Walter Reed, and one by the Beth Israel Deaconess Medical Center. Michael says they hope to have the results by the end of the year and then move into efficacy studies in Zika-affected areas. This vaccine joins one developed by Inovio Pharmaceuticals, which is moving into trials soon also, as a promising candidate for eventual public use.

Recent research has shown that the Zika virus only has one serotype, which means that even as the virus evolves different strains, these strains should all be closely enough related that one vaccine should be able to protect against all of them. This is different from, say, dengue, which has five different serotypes. Still, developing different types of vaccines offers flexibility—each one has different advantages and disadvantages. For example, the DNA vaccine is easier to make than the whole-kill, Michael says, but it’s more expensive. And the whole-kill is widely-used, so it’s more familiar to manufacturers. This is partly why the whole-kill is the one moving into clinical trials soon. (Inovio’s vaccine is a DNA vaccine.) The Army has also signed an agreement with the pharmaceutical company Sanofi Pasteur, in the hopes that the company can manufacture the whole-kill vaccine at a larger scale.

“Making 1500 doses [for a clinical trial] is one thing, making 1.5 million—there's only a handful of companies in the world that could do that,” Michael says. “The last thing you want is to have a vaccine that you show works in a clinical trial, and then Brazil says ‘Great, we want 200,000 doses,’ and we say, ‘Well you’re going to have to wait 6 months or a year.’ That's really the dilemma right now is how quickly can we translate out-of-phase-one studies into a public-health countermeasure?”