Malaria vaccines could make the disease worse
Malaria vaccines could make malaria
nastier. In mice given an experimental vaccine now in trials, the
malaria parasite evolved to get round the immunity – and in the process
caused more severe disease.
Malaria kills 2000 children every day,
sickens millions repeatedly, and helps keep tropical nations in
poverty. Yet there is still no vaccine, partly because the parasite
takes different forms as it moves from mosquitoes to human blood, to
liver cells, red blood cells and back to mosquitoes.
One malaria vaccine – RTS,S – is in large-scale trials.
It targets the liver stage of the parasite. Other vaccines in trials
target the blood-cell stage, and contain a parasite protein called
AMA-1, meant to prime the body's immune system to attack it.
These vaccines all seem likely to be
"leaky", allowing vaccinated people to still acquire and transmit some
parasites. Parasites that pass through vaccinated people this way could
start resisting the vaccine in two ways, says Andrew Read
at Pennsylvania State University in University Park. The parasites'
AMA-1 could change so that vaccine-induced immunity won't recognise it, a
process called immune escape. Or parasites may emerge that dodge
immunity in other ways, which could make the disease more virulent.
Rise in virulence
In 2004 Read tested this
by passing mouse malaria repeatedly between mice made immune by natural
infection. Those parasites indeed became more virulent, but it wasn't
clear how.
Read has now repeated the experiment
using an AMA-1 vaccine. His team passed blood-cell-stage malaria
parasites 10 times between mice that had been given the AMA-1 vaccine.
By the end, the parasites reached higher densities, and caused more
anaemia, than those passed between unvaccinated mice. Parasites from
vaccinated mice were more virulent in unvaccinated mice as well.
"The real eye-opener was that there was no immune escape," says Read. "Parasite AMA-1 was unchanged."
Boosted deadliness
Instead, the parasites had other
changes in gene activity that allowed them to escape vaccine-induced
immunity, and these changes also made them more virulent. A vaccine that
did this in people would lose its effectiveness very quickly, says
Read, while boosting the deadliness of local malaria, particularly for
unvaccinated people.
Clinical trials test whether vaccines
protect people from disease, but don't look for impacts on the actual
pathogens, apart from some that have tracked immune escape. Read says
that in future such trials should also track which genes are active in
malaria parasites in vaccinated people.
Chris Plowe at the University of Maryland in Baltimore, who works on AMA-1 vaccines, agrees. It could be difficult, however, as agencies that fund vaccine trials do not normally fund such tracking.
Journal reference: PLoS Biology, DOI: 10.1371/journal.pbio.1001368
Original from: http://www.newscientist.com/article/dn22125-malaria-vaccines-could-make-the-disease-worse.html
