THE first trial began last week of an 鈥渁ltruistic鈥� malaria vaccine that offers no immediate protection to people who are vaccinated, but which stops the disease being passed to others. David Kaslow and his team at the National Institutes of Health near Washington DC, believe that if the vaccine works it could dramatically reduce malaria鈥檚 impact on health.
Kaslow鈥檚 vaccine is designed to break the malaria parasite鈥檚 life cycle after it has caused disease, but before it can be passed on. When an infected mosquito bites a human it passes on parasites in a form known as sporozoites. After multiplying in the liver, the parasites 鈥� now called merozoites 鈥� break out and invade red blood cells. This is when people become ill.
Some of the merozoites develop into gametocytes, which are sucked up the next time a mosquito feeds, and this is where the altruistic vaccine intervenes. In the insect鈥檚 gut, the gametocytes reproduce sexually to create ookinetes. Kaslow and his colleagues manufactured a protein, called pfs-25, that sits on the surface of ookinetes. They found that when ookinetes are bound by antibodies to pfs-25, they cannot develop back into sporozoites. People injected with pfs-25 should make those antibodies, and when a mosquito bites them it will suck up blood containing both gametocytes and antibodies.
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鈥淎lthough we鈥檙e actively immunising people, what we鈥檙e really doing is passively immunising mosquitoes so they can鈥檛 pass on the disease,鈥� says Kaslow. He believes his approach has a number of advantages over vaccines that attack other stages of the parasite. Unlike the surface proteins on merozoites, those on ookinetes do not change much, so a vaccine made from them should remain effective for a long time.
A second advantage is that ookinetes sit in the mosquito鈥檚 gut for at least 24 hours giving antibodies a sporting chance of locking on to their target. By comparison, gametocytes are only present in the mosquito for about 10 minutes.
Although animals make antibodies to pfs-25 in laboratory tests, the vaccine cannot be tried out in humans until the current trial shows whether pfs-25 is safe. Kaslow is already working on second generation vaccines, which carry two proteins from ookinetes. 鈥淥ne combination already looks more promising,鈥� he says. 鈥淲e鈥檙e detecting even fewer of the parasites 鈥� inside the mosquitoes.鈥�
Kaslow is wary of sounding over optimistic about the vaccine. 鈥淲e will need to test it in an endemic area to see what effect it has on levels of malaria there,鈥� he says. He hopes to conduct a trial in Mali, West Africa.
鈥淲e have to make sure that people understand that if they get ill themselves, it doesn鈥檛 mean the vaccine hasn鈥檛 worked,鈥� says Kaslow. 鈥淚t鈥檚 a bit like vaccinating people in developed countries against rubella. The real purpose is to prevent pregnant women getting the disease, not the individual,鈥� he says. 鈥淧eople don鈥檛 always realise that.鈥�
The concept of the altruistic vaccine 鈥渋s intellectually attractive鈥� says Adrian Hill from the University of Oxford. 鈥淲e don鈥檛 know if it will work, but all avenues need exploring.鈥� (see Diagram).
