Zika vaccine protects mice: but may increase risk of dengue
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 vaccine: needs more work - Sujata Jana/EyeEm/getty
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
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
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
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
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
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