Zika outbreak: Monkey study suggests infection lasts longer in pregnancy than thought

Researchers infected pregnant monkeys with the Zika virus to learn how it harms developing fetuses — and in a highly unusual twist, the public can get a real-time peek at the findings.

Rhesus macaque monkeys make a good model for studying how Zika infects people

Researchers infected pregnant monkeys with the Zika virus to learn how it harms developing fetuses — and in a highly
unusual twist, the public can get a real-time peek at the findings.

Among the first surprising results: While most people harbour Zika in their bloodstream for only a week or so after infection, the virus lingered in one pregnant monkey's blood for 70 days and in another for 30 days.

A bit of good news: Tests with non-pregnant monkeys suggest one infection with Zika protects against a second bout later on.
We are in a race against the virus, a race against time.- Koen Van Rompay

Rhesus macaque monkeys make a good model for studying how Zika infects people, researchers at the University of Wisconsin-Madison concluded Tuesday in Nature Communications. But what's novel is that the team is posting its raw data online right away — even ultrasound images of developing monkeys that they acknowledged at the time "can elicit stronger emotions than looking at relatively sterile charts" — so that normally competing research labs can work together to speed discoveries.

That collaboration will help "use as few animals as possible to answer important research questions," lead researcher David O'Connor, a pathology professor at UW-Madison, told reporters. "We hope this will encourage others to make their data available in real time to accelerate the response time to Zika virus and other outbreaks in the future."

A handful of other labs have joined in the movement to share their own data from Zika-infected monkeys in real time.

"This is how research should be, especially for emerging diseases that are causing so many problems," said Koen Van Rompay of the California National Primate Research Center at the University of California, Davis. He and O'Connor have begun consulting to avoid duplicating experiments. "We are in a race against the virus, a race against time. We should not be competing against each other," Van Rompay added.

The Zika virus, which is spread mainly by a tropical mosquito, is causing an epidemic in Latin America and the Caribbean. It causes only a mild illness, at worst, in most people but can cause severe brain-related birth defects if woman are infected during pregnancy.

No one knows how big the risk is, or how to tell which pregnancies will be affected.

Protective vaccine hints

O'Connor's team gave monkeys a skin jab with a strain of Zika virus to mimic a mosquito bite. Tuesday's paper compiles results from eight animals. Much like people, the six non-pregnant monkeys cleared Zika out of the bloodstream fairly quickly, in about 10 days.

And when researchers attempted to infect them with the same strain 10 weeks later, they didn't get sick — evidence that it should be possible to design a protective vaccine, O'Connor said.

"We don't know how long this immunity lasts," cautioned study co-author Dawn Dudley, but that's a key question for women in countries hard-hit by the virus.

Elsewhere on Tuesday, mice given a single shot of one of two experimental Zika vaccines were completely protected when exposed to the virus one to two months later. It's a promising sign that similar vaccines under development for humans will protect against Zika, U.S. researchers said.

"The new mouse model should be useful for comparative assessments of the large range of vaccine candidates now being designed," said Professor Adrian Hill, director of Oxford University's Jenner Institute, which did not conduct the mouse study but is also developing Zika vaccines.

In the mouse study, published in the journal Nature, a team led by Dr. Dan Barouch of Beth Israel Deaconess Medical Center and Harvard Medical School, tested two different vaccine candidates in a strain of mice that develops Zika symptoms.
One candidate, a DNA vaccine, was developed by Barouch and colleagues. It contains bits of genetic material from a Zika virus strain from Brazil.
The other was made from a purified but inactivated version of the Zika virus from Puerto Rico. That vaccine was developed by researchers at Walter Reed Army Institute of Research in Silver Spring, Md.

Does longer virus presence in blood relate to birth abnormalities?

Mice given either type of vaccine were 100 per cent protected from Zika after a single shot. Unvaccinated mice that were exposed to the virus all developed symptoms of Zika.
Both types of vaccines — DNA and inactivated virus vaccines — have been successfully developed to prevent infection from viruses related to Zika, including West Nile and dengue.
"We need to be cautious about extrapolating data from a mouse model into humans," Barouch said. But the fact that the vaccines protected mice and that their antibodies protected other mice from Zika was grounds for optimism over the development of a Zika vaccine, he said.

Another big issue with the monkey research is why the two pregnant monkeys, infected during the first trimester, had infections linger drastically longer — something reported so far in only one human case, which ended in abortion.

When those monkey babies are delivered by C-section and euthanized next month, their tissues and placenta will be carefully examined for Zika. One theory is that if a fetus is infected, it will pump virus back into mom's blood, O'Connor said.

"We might hypothesize that the pregnancy with the longest duration of extended viremia is more likely to have abnormalities detected at birth, but right now that's simply a hypothesis," he cautioned.

O'Connor's team also infected two more monkeys in the third trimester of pregnancy; tests on those babies' brains and other tissues are under way.

With files from Reuters