Potent Buzz: A Whole-Parasite Vaccine

“Mosquito Crossing” warns the yellow road-caution sign. The attention-grabbing notice hangs on the door to the “challenge room” of Chris Plowe’s insectarium, at the University of Maryland, Baltimore. Inside, volunteers roll up their pant legs while researchers press a Dixie cup with four or five malaria-infected mosquitoes against their ankles. The blood-swollen insects are collected for analysis and blood samples are drawn from the volunteers.

The work is part of a “challenge study”—the first clinical trial of a promising “attenuated sporozoite” vaccine being developed by Sanaria Inc., a company headed by Plowe’s early mentor, former Navy researcher Steve Hoffman. There are dozens of other vaccine candidates in various stages of development—the farthest along being GlaxoSmithKline’s RTS,S vaccine, now in Phase III tests at 11 African sites—but Plowe says “the Sanaria vaccine is the only vaccine that uses the whole [parasite] organism.” The others, he says, which focus on one antigen variant, “are like trying to stop an elephant with a BB gun.”

The concept, Hoffman explains, is to use sporozoite-stage parasites—an early, motile stage that infects the liver—that have been weakened (attenuated) by exposure to radiation. Although the weakened parasites cannot complete their life cycle, they survive long enough to awaken the human immune system and confer protection against malaria. The overall challenge study is being led by clinical investigators Kirsten Lyke at the University of Maryland’s Center for Vaccine Development and Judith Epstein at the Navy’s research center. Right now, Plowe’s is a supporting role but eventually he will design and implement studies of the vaccine in Africa.

In a sense, the current challenge trial is part of a Maryland tradition. The first malaria vaccine trials in humans—with an attenuated sporozoite vaccine developed by researchers at New York University—were done in the early 1970s by University of Maryland professor David Clyde. (Previous malaria vaccine research had been done on ducks and rodents as far back as the 1920s.)

“The early-1970s Maryland vaccine trials proved the principle that sporozoites can give protection,” says Hoffman. “But they couldn’t produce sporozoites that met regulatory standards—that is, sterile, pure, highly attenuated, and still potent.” That is what Sanaria is now trying to do in a painstaking process that is taking years to develop and test.

Plowe says he’s “excited about taking a whole-organism vaccine to Africa” for clinical trials, which probably will begin within a few years. “With the attenuated sporozoite vaccine, even if you have diversity in one antigen, hopefully you’ll have 10 other antigens. You are taking it from the genetic level to the genomic level.”

Hoffman says Plowe is the right researcher to design and implement vaccine trials in Africa and apply genomics to understand how a whole-parasite vaccine works. “He has the capacity to work with not only his biomedical colleagues but also the people in Africa who suffer the most from this disease.”

-- Robert Koenig
HHMI Bulletin, August 2010

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