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Today, a human trial for a malaria vaccine reported up to 100% protection for ten weeks following the last dose, a potential breakthrough for a vexing disease.

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While this vaccine has been trialed before, it has never been this effective. The key appears to be how the vaccine was delivered—directly into the bloodstream as opposed to into a muscle, as most vaccines are.

The new technique, which delivers the vaccine into the vein, is similar to drawing blood.

The trial consisted of 35 participants who had never been exposed to malaria. They were first injected with varying doses of the vaccine, which uses weakened malaria-causing parasites

Plasmodium falciparum

, along with chloroquine, an antimalarial drug. Participants were then infected with the same strain of malaria used in the vaccine. The results were published today in the journal Nature.

“I think it’s among some of the best malaria protection data,” said Dan Barouch, a professor of medicine at Harvard Medical School, “but we have to keep in mind it is in a controlled human challenge study. So, whether it can be extrapolated for protection against malaria in the field remains to be determined.”

In earlier trials, scientists used weakened live malaria parasites delivered via mosquitoes to induce an immune response, which then imparted protection in more than 90% of participants. This study experimented with direct venous inoculation (DVI), a different method of administering vaccines that injects the vaccine directly into an individual’s vein.

Dr. Stephen Hoffman, CEO and chief scientific officer of Sanaria, Inc., and the lead author of the study, says DVI is similar to drawing blood. While it requires more skill than the standard poke-in-the-arm immunization technique, he said that DVI is less painful and less uncomfortable. “Thus far, it has proved to be extremely well tolerated, much better tolerated than when you give a vaccine in your muscle—and safe, with no adverse events associated with it,” Hoffman said.

Researchers found that three high doses of the vaccine administered every four weeks delivered the best results. Nine out of the nine participants (100%) given high doses were immune for at least ten weeks after the final dosage. Lowering the dose significantly reduced the efficacy, and speeding it up slightly—with doses delivered three times every five days instead of every week—dropped the number protected to five out of eight participants (63%).

DVI is logistically more difficult than traditional routes of immunization, Barouch said, which may pose challenges in moving the vaccine out of the lab. “There’s a number of immunologic reasons why they chose to administer the vaccine intravenously, but clearly that will be a downside in terms of upscaling the vaccine approach.”

Last year, the countries spent hundreds of millions of dollars on malaria control efforts. And despite the efforts and investments of global health organizations, there were still an estimated 214 million cases of malaria and 438,000 deaths, more than two-thirds of which were children under the age of five. As mosquitoes develop resistance to insecticide, vaccines remain the most cost-effective, long-lasting approach to fight and possibly eliminate the disease.

Though these findings are a step in the right direction, the vaccine still has more hurdles to surmount, including research into whether the DVI can be used as part of a mass vaccination strategy. In future clinical trials, Hoffman and his colleagues said they will explore how long the protection lasts, whether it’s effective in diverse populations, and how it responds to different forms of exposure and strains of malaria.

“We want to prove, incontrovertibly, before we unleash a vaccine, that the vaccine has the performance characteristics that no one will argue about,” Hoffman said. “This is the best result so far, but it’s still a very tough parasite with a tough problem worldwide. We’re under no illusions that this won’t be difficult.”