Zika vaccine protects mice: but may increase risk of dengue

by Debora Mackenzie

If only it were that simple. Just one dose of a newly developed Zika vaccine gives mice complete immunity to the disease. Safety trials in people are planned for October.

But some researchers warn there might be a major drawback – the vaccine might put people at greater risk from another more common virus, dengue. But the good news is that a more precisely targeted vaccine may eventually work for both diseases.

Zika virus has invaded 47 countries in the Americas since 2015. It often causes no symptoms, or fairly mild ones. But in some people Zika triggers neurological damage, and it can severely disable a developing fetus.

Hence, the need for a vaccine. This week, Dan Barouch at Harvard Medical School and his colleagues report that their vaccine made from the whole, killed virus left mice immune to a normally fatal dose of Zika.

Like most vaccines, this one works by raising antibodies in the infected individual. But those antibodies could also create a problem. Zika is closely related to the dengue virus, a much more familiar threat. Gavin Screaton and colleagues at Imperial College London reported last week that antibodies to dengue cross-react strongly with Zika.

Blood cell hijacked

This is not a helpful response. Dengue comes in four strains. Antibodies to one strain bind to the other three, but do not “kill” or neutralise them. Instead, they attract white blood cells such as macrophages, which engulf the virus whole – but the virus hijacks the blood cell’s machinery and replicates.

This “antibody-dependent enhancement” lets the virus reach higher levels in the body than it would do otherwise. People are often mildly ill with the first strain of dengue they catch, but if they catch one of the others, the antibodies to the first strain enhance the second infection, and they may become severely sick or even die.

With the help of a library of dengue antibodies extracted from people with the disease, Screaton’s team discovered that the dengue antibodies enhanced Zika infection in cultured cells. It was as if Zika were a fifth strain of dengue.

If antibodies to dengue bind to Zika, then antibodies to Zika bind to dengue. “It is possible that vaccines may raise antibodies capable of promoting antibody-dependent enhancement,” says Screaton, meaning Zika vaccination could make a subsequent dengue infection worse.

In further experiments, the team found that antibodies that trigger enhancement dominate the human immune response to the live virus, so people vaccinated with whole dead virus may respond in the same way.

It will be important to test all this thoroughly before releasing any Zika vaccine, since regions of the world with Zika also have dengue.

Trial and error

Nelson Michael of the Walter Reed Army Institute of Research in Silver Spring, Maryland, says that the trial Zika vaccine will be tested on mice and monkeys that already have antibodies to dengue, to see if that interferes with the vaccine. But they will have to give a Zika-vaccinated animal dengue to see if the vaccine makes that illness worse.

The first human trials will be done in the US in October with people at low risk of subsequent Zika or dengue infection, says Michael. But when trials move to virus-affected regions, “we will carefully track our volunteers”.

The good news is that not all antibodies are equal. The team found that antibodies that bind to one particular bit of dengue’s main surface protein enhanced Zika infections in cultured cells. But antibodies to another bit, called EDE, killed all strains of dengue and Zika. They even blocked enhancement of Zika infection caused by other dengue antibodies.

The Imperial team think a vaccine that elicits immunity only to EDE might work for all strains of dengue and Zika, but that could take time to develop. In the meantime, artificially produced antibodies to EDE might protect pregnant women from Zika.

- New Scientist