Most malaria vaccines under development work by including genetically engineered versions of just a handful of the thousands of proteins of the Plasmodium parasite. Those modified proteins are designed to trigger an immune response to Plasmodium, after it’s passed into the host’s bloodstream by the bite of an infected mosquito.
In contrast, says researcher Robert A. Seder of the U.S. National Institute of Allergy and Infectious Diseases, this new vaccine includes a deactivated version of the entire parasite.
“So instead of picking out one or two or three genes,” he says, “you have the potential for what we call breadth – generating an immune response that would be broad rather than narrower. And so that would be a good thing.”
Plasmodium goes through many stages in its life cycle. To make this vaccine, scientists use the parasite at the stage – called the sporozoite – when it’s ready to infect new hosts. They remove the sporozoite from the mosquito’s salivary glands and then subject it to radiation.
That weakens it, so it can’t cause malaria symptoms, and can’t be transmitted via mosquito to another person, either.
This concept has been known since the 1960s, but Seder says there were practical obstacles that prevented the development of a malaria vaccine.
“The major breakthrough here was that my collaborator, Stephen Hoffman at [vaccine company] Sanaria, developed a method where he could isolate the sporozoites and purify them so that they could administer it as a vaccine to humans. And no one thought that that was possible,” he explained.
And no one knew if the weakened sporozoites would jump-start the immune system to protect against malaria.
To find out, researchers used human volunteers. The vaccine was injected into their skin with a needle, to simulate the bite of a mosquito. From a safety standpoint, the results were good – there were only relatively minor side effects. But a vaccine must be safe and effective, and this one just wasn’t very effective. Only two out of 44 volunteers who got the vaccine were protected when bitten by malaria-infected mosquitoes.
To find out why, the researchers then switched to laboratory animals, and Seder says they concluded that the problem was the way the vaccine was administered.
“Had [Hoffman] given [the vaccinations] in the vein, intravenously, directly in the blood, rather than through the skin, he would have gotten much higher immune responses.”
That would be unusual for a vaccine, which is typically given by mouth or as a skin or muscle injection. It also might complicate mass vaccination programs, if the vaccine goes into general use.
Cost is also an issue, but researcher Seder says it’s too soon to know how the vaccine will be priced – assuming it is effective.
The next stage of human testing – using intravenous administration – is due to start in October, 2011.