Injecting live malaria parasites into people safely immunizes them from the disease

A malaria vaccine approach that might strike some as radical has had stunning success in a small human trial. Its developers contend the unusual strategy could serve as a backbone of campaigns that attempt to eliminate the devastating disease.

“It’s an extremely exciting piece of work,” says Pedro Alonso, who heads the Global Malaria Programme at the World Health Organization (WHO) in Geneva, Switzerland. “It’s not the most conventional approach of immunization, but given the magnitude of the malaria problem, it’s well worth pursuing.”

Vaccines typically train the immune system with a harmless version of the disease-causing organism. But traditional malaria vaccines that contain a weakened version, or just pieces of, the Plasmodium parasite that causes the disease have had lackluster success.

So researchers from Sanaria, a biotech company that makes various malaria vaccines in Rockville, Maryland, and their collaborators at the University of Tübingen in Germany upped the ante: They injected live Plasmodium sporozoites—the form of the parasite that establishes the infection—into the veins of nine people. The volunteers got three injections at 4-week intervals. They also took antimalaria chloroquine pills shortly before, during, and shortly after receiving the sporozoites, which crippled the parasite in the liver before it could return to the bloodstream in a disease-causing form.

When the researchers “challenged” the nine vaccinated participants with the sporozoites 10 weeks later and did not give them chloroquine, no one became infected and no serious side effects occurred, they report today in Nature . In contrast, 13 people who were challenged and did not receive the vaccine all had the parasites in their blood (at which point they received treatment).

The success with live sporozoites is not a first: In 2009, researchers reported 100% protection in 10 volunteers taking chloroquine who were “vaccinated” by having mosquitoes infected with P. falciparum intentionally bite them. But the team admitted that using mosquitoes as the delivery vehicle does “not represent a widely implementable vaccine strategy.” (To make the chemoprophylaxis vaccine—or CVac, as Sanaria calls it—the company harvests and purifies sporozoites from the salivary glands of mosquitoes.)

The researchers don’t know how long protection from CVac will last. Adults who have built up natural immunity to malaria after surviving infections lose that protection within a few years if they move to an area without malaria transmission.

However, modeling shows that if 90% of a population received injections of these sporozoites at the proper dose, coupled with mass “chemoprophylaxis” with drugs like chloroquine for only 6 months, it would “halt malaria and eliminate the parasite,” says Sanaria’s founder and CEO Stephen Hoffman. “We think that would be revolutionary,” he says, noting that “mass drug administration” to prevent malaria already takes place in some locales.

That may not be a realistic strategy, cautions epidemiologist Marcel Tanner, who heads the Swiss Tropical and Public Health Institute in Basel and has worked in Africa for 38 years. “If you don’t have enough dirt on your shoes to know how this goes, you can overlook simple operational problems.” For example, failure to properly follow the sporozoite injections with antimalarial treatment could lead to serious illness and even death. “I could imagine many ethical boards and governments would have hesitations,” Tanner says.

Still, he says, CVac could work well for travelers or military troops temporarily visiting malarial areas—and maybe on an island or in other well-defined areas where you can “vaccinate and treat like a military action.”