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January 5, 2017

A Genetically Modified Malaria Vaccine Has Passed an Important Hurdle

  • Other
  • Genetics/Genomics

MIT Technology Review – It seems a primitive way to fight one of the world’s worst diseases, but 10 volunteers have been bitten by malaria-carrying mosquitoes in an effort to test out a new kind of genetically modified vaccine. So far, so good: no one got sick, and all 10 subjects developed antibodies, suggesting the new vaccine was doing its job.

Researchers led by Jim Kublin at the Fred Hutchinson Cancer Research Center in Seattle knocked out three genes in the parasite Plasmodium falciparum, which causes the type of malaria most commonly found in Africa. Previous testing in mice showed that deleting just those genes was enough to prevent the parasite from progressing through its life cycle—infected mice developed antibodies but never got sick. They reported the results of the first trials in people today in the journal Science Translational Medicine.

It’s a promising step for a vaccine that is badly needed—in 2015, the World Health Organization estimated that 214 million people got malaria and 438,000 died from it.

Several malaria vaccines are in development, but they all come with big drawbacks. One, called RTS,S, uses a genetically modified protein from P. falciparum to condition the immune system against the parasites. It has undergone large human trials and it’s scheduled to be rolled out in three countries in sub-Saharan Africa in 2018. But it’s only effective in about a third of patients.

Another method in trials uses radiation to damage parasites’ DNA and weaken them. They are then injected. The vaccine, called PfSPZ, has been shown to provide lasting protection in more than half of people, but only if they went through four rounds of injections.

Irradiation damages DNA at random, whereas targeted gene deletion achieves a consistent result—that’s likely why the volunteers who were bitten all had the same reaction. That makes this most recent vaccine particularly attractive.

But it’s early days. For one thing, volunteers exposed to the parasites with deleted genes were never infected with full-strength bugs to see if their immune systems would fend them off. That crucial next step is due to occur sometime next year, according to Science. If all goes well, the vaccine could then move into large-scale trials.

Until then, a vaccine that helps half, or even a third, of people who get it isn’t ideal, but it would still save thousands of lives. And it would be a welcome addition to other, more prosaic tactics for fighting malaria, like distributing bed nets, that have made progress against the disease.

If that feels incremental or unsatisfying as a solution to one of the world’s greatest challenges, you could always just engineer the mosquitoes themselves out of existence.