In a Phase I trial, a vaccine made up of weakened immature malaria parasites provided high levels of immunity against malaria infection. Scientists reported the results in the Aug. 8, 2013, online issue of Science.

The catch? It's an intravenous vaccine.

The intravenous administration is, at least for the time being, critical to making the vaccine effective. Previous studies had shown that delivery into or under the skin provided only weak immunity. (See BioWorld Today, Sept. 9, 2011.)

The apparent reason, co-author Stephen Hoffman told BioWorld Today, is that much of the immune response to malaria parasites is generated in an organ not generally thought of as part of the immune system – the liver.

The malaria parasite Plasmodium falciparum has a complicated life cycle, moving between different sites in two different hosts. But when a human becomes infected through the bite of an infected mosquito, sporozoites – immature P. falciparum parasites – will first take up residence in the liver.

The vaccine that Hoffman, who is CEO and chief scientific officer of biopharmaceutical company Sanaria Inc., and his colleagues are reporting on is made up of live but weakened sporozoites that also need to get to the liver. And at the current stage, at least, the best way by far to get them there is through intravenous delivery.

Hoffman stressed that the intravenous injection should not be thought of as being particularly similar to blood draws or intravenous lines. The volume of material that needs to be injected is small – at most, half a milliliter, and sometimes considerably less than that. In comparison, the minimum volume of a blood draw is 7 to 10 milliliters.

That small volume allows the vaccine to be delivered via a much smaller needle than what's used for blood draws, Hoffman said. "You can't even feel it going in."

In the work now published in Science, Hoffman and his colleagues vaccinated 40 healthy adult volunteers who had never had malaria with various doses of the vaccine, and then exposed them to a controlled malaria infection by allowing five infected mosquitoes each to bite them.

Of subjects that had been vaccinated with high doses of vaccine, only 20 percent became infected, and repeated administration of the highest dose resulted in complete protection of six volunteers. That contrasted with a more than 90 percent infection rate for those who received low doses of vaccine, or no vaccine at all.

Hoffman said with those results, the team has achieved its goal: "to prove once and for all that we can get high-level protective immunity against malaria with a vaccine." In earlier work, the team had defined that goal as the development of "a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in >/= 80 percent of recipients." (See BioWorld Today, Sept. 9, 2011.)

Even though the injections are easy as far as intravenous injections go, one of the goals of the team is to see whether the vaccine can ultimately be made sufficiently effective even if delivered into or under the skin.

In an interview posted to the Science podcast, corresponding author Robert Seder, who is at the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, acknowledged that the possibilities for intravenous administration of a preventive vaccine, particularly for infants, "may be limited."

But he also pointed out that the current trial showed that there is an immune threshold, and that means that "other routes, with perhaps higher doses of the vaccine, might be effective." Another possibility, he said, would be to "develop devices to deliver the vaccine such that it would mimic an intravenous administration."

For the time being, though, the first generation of the vaccine that Sanaria intends to take to the FDA, which would be aimed at travelers, military personnel and mass administration for geographically limited malaria eradication campaigns, will be an intravenous form.

The trial is only one of half a dozen similar trials slated to start within the next few months, in the U.S., Germany and several African nations – Tanzania, Mali and Equatorial Guinea.

Those trials, Hoffman pointed out, are being funded by different funding agencies, rather than by Sanaria itself.

"It's a demand-driven clinical trial program," he said.