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Caused by Plasmodium parasites, malaria affects more than 200m people annually. According to the World Health Organisation, in 2010 malaria >killed 660,000 , most of them children. GlaxoSmithKline’s Mosquirix is the most advanced malaria vaccine currently being tested. It protects against Plasmodium falciparum , the most deadly of the parasites.
But, as Brian Greenwood of the London School of Hygiene and Tropical Medicine told The Conversatio , “Mosquirix is only about 50% effective when given to older children and even less effective (about 30 per cent) when given to young infants with routine vaccines. A better vaccine with a higher level of protection is needed.”
The new vaccine, dubbed PfSPZ, has been developed by Sanaria, a US biotech firm, in collaboration with the National Institutes of Health (NIH). Like Mosquirix, it attacks the first stage of malaria called “pre-erythrocytic”, and may stem the disease before symptoms show. But unlike Mosquirix, which is made of proteins from the parasite’s surface, PfSPZ uses consists of sporozoites, a young form of the malarial parasite, that have been weaked by irradiation.
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Sanaria’s concoction was tested in 44 volunteers two years ago by delivering the sporozoites through an injection into the skin. But only two of them developed the required immunity. Later animal studies by Robert Seeder of NIH showed that delivering the vaccine by injecting directly in veins was more effective.
This is what Sanaria have done in the new trials. Each of their injections consisted of 135,000 irradiated sporozoites. Only three of the nine volunteers who were given four of these injections at one month intervals developed malaria. None of the six who were given five doses developed the disease.
The number of patients involved is tiny. Greenwood warns, “This is only a proof of principle study, although a very important one, and the experiment will need to be repeated on a larger numbers of subjects before it can be taken into field trials in malaria endemic areas.”
And scaling up is not going to be easy. Currently, the sporozoites are extracted from mosquitoes manually. Sanaria has employed 15 “dissectors” who can each tear open about 150 mosquitoes per hour. The process will need to be automated if PfSPZ is to make it to the market.
The limitations go further. PfSPZ needs to be stored in liquid nitrogen containers. Without five doses it cannot produce 100% protection. Those doses need to be delivered intravenously, which is difficult to do in infants and requires trained professionals for older children .
All this makes the vaccine, in its current form, expensive and impractical for a disease that affects the world’s poorest people. “However, the problems are not unsurmountable and there may be technical ways of addressing this challenge,” Greenwood said.
Adrian Hill, professor of human genetics at the University of Oxford, welcomes Sanaria’s vaccine but feels he may have a better solution. His research group is working on combining Mosquirix with another vaccine that he believes could be as effective as PfSPZ and won’t have the same limitations.
“Mosquirix attacks the first half of the pre-erthyrocytic stage,” he said. “Our vaccine attacks the second half of that stage using a viral vector to deliver the antigen (a molecule that activates the immune system). It is this combination that may do the trick.”
Sanaria’s results, published in the journal >Science today, are at the very beginning of the vaccine development. There are many other vaccines at various stages of development intermediate between that of the Sanaria vaccine and Mosquirix. “These other vaccines may come to market quicker than PfSPZ, given its limitations,” said Hill, who is optimistic something good will emerge from them. “If all goes well, by 2020, we should have a cheap and effective malaria vaccine.”