The rapid spread of the Zika virus over the past year has caused thousands of babies in the Western Hemisphere to be born with abnormally small heads, terrifying women of child-bearing age and causing concern among public health officials.
Now, a trio of UNM scientists is racing to develop a vaccine using a novel technology that they hope will trick the immune system into attacking and neutralizing the mosquito-borne microbe.
David Peabody, PhD, and Bryce Chackerian, PhD, professors in the Department of Molecular Genetics and Microbiology, have teamed up with Steven Bradfute, PhD, an assistant professor in the Division of infectious Disease and the Center for Global Health in the Department of Internal Medicine. Their project is getting a jumpstart with funding from UNM’s Clinical & Translational Science Center (CTSC).
“We’ll be able to do an awful lot of this in a year,” Peabody says. “That’s to get an idea whether it works in a mouse. It will take longer to test in nonhuman primates, and ultimately, humans. We have no idea whether it will reach that stage, of course.”
The project starts with a key technology Peabody developed. He took a bacteriophage – in this case, a virus that infects e. coli bacteria – and figured out how to produce its outer shell while eliminating its genetic material. What remains is a non-infectious particle that resembles a microscopic soccer ball.
Due to its unique shape, our immune systems identify this inert protein sphere as a virus, triggering the production of virus-killing antibodies. “When Bryce and I got together about 10 years ago, we realized this could be a vaccine platform,” Peabody says.
He and Chackerian are trying attach just a small piece of the Zika virus to the surface of the virus-like particle. They hope the human immune system will develop a unique antibody in response to the vaccine that neutralizes the active virus.
“We try to look for the Achilles heel of the pathogen,” Chackerian says. The trick lies in figuring out what part of the pathogen to attach to the virus-like particle. One approach is to generate a “library” of virus-like particles displaying fragments of Zika proteins, testing them to see whether they interact with antibodies from people who have survived Zika infections.
“We can take antibodies that are protective against Zika virus and use them as a screening tool,” Chackerian says. “We can pull out particles that display portions of the Zika protein that could potentially be protective.”
Identifying a candidate vaccine should happen relatively quickly. The next step lies in confirming that it stimulates an effective immune response and actually prevents disease. That’s where Bradfute comes in.
Zika was little studied until recently because it typically causes mild – or no – symptoms in the people it infects, says Bradfute, who has extensive experience working with exotic tropical diseases, like Ebola. It was first identified in 1947 in monkeys in the Zika forest of Uganda.
“The first human infections were found in Nigeria in the 1950s,” he says. “From then on, every couple of years there would be small groups of people getting infected, but never more than a dozen or so, and none of these people would get very sick.” Most developed a fever or rash that quickly went away.
“Then in 2007, on a Micronesian island called Yap there was the largest Zika outbreak,” Bradfute says. “It infected a few thousand people, which was three-quarters of the island. But about 80 percent of the people didn’t have any symptoms.” Another outbreak in 2013-2014 infected about 30,000 people in French Polynesia.
“That was the first inkling something wrong was happening,” Bradfute says. Some patients were developing Guillain-Barré syndrome, a rare neurological disorder. And then the Zika epidemic struck Brazil in 2015. “That’s the first time they started seeing the microcephaly cases in pregnant women,” Bradfute says.
Timely funding from the CTSC “was really incredible,” Bradfute says, because it typically takes time to qualify for research money through the National Institutes of Health. “Getting something to start rapid studies on this was really great,” he says.
“Dave and Bryce generate the vaccine,” he says. “They’ve got the technology and they can tailor the vaccine specifically to Zika. What we do is analyze the immune responses. We determine how much a response we get and whether or not it protects from infection.”
Bradfute and his team are studying Petri dish cultures to see how the virus infects and kills human cells. When they have a candidate vaccine in hand, they can introduce it into the cell culture to see whether it’s protective, and at what concentration.
“The other component is we can challenge mice with the live virus and see how well the virus replicates in their blood,” Bradfute says. A successful immune response in mice would be good news, because the immune systems in mice and people are pretty similar.
Bradfute says that because the stakes are so high, the UNM team is in a race with researchers around the world. “I knew nothing about Zika virus until last November,” he says. “The pace at which discoveries have been happening is really incredible.”