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VACCINES against malaria that seem to work brilliantly at first might end up
backfiring, a new computer model shows. Some vaccines might hasten the evolution
of nastier strains of the parasite which causes the disease.

鈥淪ome could work really well but have bad long-term consequences,鈥� says
Andrew Read of Edinburgh University. 鈥淣astier strains might take decades to show
耻辫.鈥�

Knowing in advance which ones are risky would allow vaccine developers to
adjust their treatments, monitor the evolution of the parasite over time and
prepare contingency plans to thwart any virulent new strains that show up.

Most super-strains die out almost as soon as they evolve because they kill
any humans they infect. Milder strains dominate because they infect people
without killing them, buying them time to be retransmitted.

But mathematical models developed by Read and his team show that vaccines
could upset this balance by protecting people against any virulent strains that
evolve. This would allow these strains to thrive while the body鈥檚 immune system
picks off the milder ones. Mosquitoes that feed off the infected blood will then
pick up the deadlier strains from vaccinated people and spread them to
unvaccinated people鈥攚ith lethal effects.

The safest vaccines would turn people鈥檚 bodies into a dead end for the
parasite. This means blocking either the infectivity of the Plasmodium
falciparum parasite that mosquitoes inject into the blood, or its means to
escape from the body.

Read says the best place to do this is in the liver, where the immature form
of the parasite, called sporozoites, lodge and mature. The parasites then
re-enter the blood, causing a full-blown infection as they release
fever-inducing toxins. They then mature into gametocytes which are picked up by
feeding mosquitoes, completing the cycle. Wiping out the sporozoites in the
liver would break the cycle.

A vaccine that does exactly that has just completed a major trial in Gambia
(The Lancet, vol 358, p 1927). The vaccine, code-named RTS,S/AS02,
reduced the risk of infection by between a third and a half. 鈥淭his is the sort
of vaccine that generates least evolutionary risk,鈥� says Read.

Other 鈥渓ess risky鈥� vaccines under development include ones that prompt the
immune system to destroy parasites before they become transmissible.

The more risky vaccines, according to Read, are those that target other
stages of the parasite. They slow down the infection instead of getting rid of
it altogether. The same applies to vaccines that generate antibodies to 鈥渕op up鈥�
the toxins which cause fever. Again, these let the parasites survive and
evolve.

Read鈥檚 analysis predicts that these last two types of 鈥渞isky鈥� vaccine could
double the virulence of the parasites in around 30 years. But he stresses that
he鈥檚 not against them, and applauds the early promise they鈥檙e showing.