Shivering beneath a mountain of heavy blankets pulled up to my eyes, I was convinced I would never warm up again. Then, seemingly minutes later, I was kicking sweat-drenched blankets to the floor as my body was overcome by a burning fever that no amount of ibuprofen could cure.
I felt nauseous, and my mind wandered far beyond the corridors where I lay confined to a hospital bed. Throughout the torturous night, I tossed on the twin-size bed, drifting in and out of consciousness even as my body remained defiantly awake.
I had malaria, there was no doubt.
Later, as the medication battled the parasites that had infested my liver, I stared at my unkempt reflection in the bathroom mirror and wondered: Why did I do this?
It was, in fact, both desperation and curiosity that landed me in that hospital bed. In September 2011, I was a journalism student with an unsustainable part-time job that barely covered the cost of my groceries. I had just entered my senior year at American University and was living in a modest apartment five minutes from the main campus in Washington, D.C. While absentmindedly browsing through job and volunteer opportunities on Craigslist one afternoon, I stumbled across a posting from the National Institutes of Health in Bethesda seeking participants for a malaria study.
A mosquito-borne disease that affects more than 250 million people a year, malaria appears to have been around since humans migrated out of Africa some 60,000 years ago, according to a 2010 Current Biology report. The Plasmodium parasite that causes the illness killed an estimated 660,000 people in 2010 alone, most of them children in Africa, a region that accounts for 91 percent of malaria deaths.
Attracted by the idea of participating in a potentially groundbreaking study, as well as the promise of unspecified financial compensation, I volunteered to test a preventive vaccine at NIH’s Vaccine Research Center (VRC). Called “PfSPZ,” the vaccine was developed by Sanaria Inc. to combat Plasmodium falciparum, the deadliest of the four species of malaria that commonly infect humans.
Dr. Stephen Hoffman, former chief of the U.S. Navy’s malaria research program, founded the Rockville-based biotech company in 2003 to combat the disease. He wanted to expand on earlier research that showed animals and humans could receive protection against the disease through exposure to hundreds of thousands of weakened parasites.
In 1967, Dr. Ruth Nussenzweig, a scientist and professor at New York University’s School of Medicine, had irradiated malaria-infected Anopheles stephensi mosquitoes, which weakened the parasites and prevented them from replicating. After the irradiated mosquitoes feasted on lab mice, the rodents developed an immune response that effectively protected them against the disease.
Over the years, scientists tested this idea on human volunteers, and studies showed that receiving weakened parasites from at least 1,000 irradiated mosquitoes could generate the production of antibodies in the liver and provide protection against the disease. To verify the procedure’s efficacy, Hoffman used himself as a test subject in the mid-1990s and allowed 3,000 irradiated mosquitoes to bite him at various intervals. In the end, he was rendered immune to the disease.
Of course, subjecting millions of people to the bites of thousands of irradiated mosquitoes is neither practical nor realistic (not to mention unpleasant). So scientists have developed subunit vaccines, using the antigens but not the entire parasite. One of these, “RTS,S”—developed by the Silver Spring-based Walter Reed Army Institute of Research and the pharmaceutical company GlaxoSmithKline—entered Phase III testing in 2009, with 15,460 participants enrolled in 11 trials throughout sub-Saharan Africa. Results of the trial, which was completed in January 2011, made headlines this past fall. RTS,S showed protection rates of 27 percent in African children under age 5 months, who are among the most vulnerable to the disease, and 46 percent in African children between 5 and 18 months, making it the most promising vaccine to date. Even as some were hailing it as a triumph, though, others were questioning whether those figures could be deemed sufficient.
A decade earlier, Hoffman became convinced he could use the whole-parasite approach to engineer a groundbreaking vaccine. He quit his job at Celera Genomics, the genetic sequencing corporation founded in Rockville by J. Craig Venter. And with the help of his wife and son, who had just graduated from college, Hoffman launched his own company from the breakfast room of his Gaithersburg home.
Hoffman named the company Sanaria, which means “healthy air” in Italian (mal’aria means “bad air”). The firm, which was initially based in a modest, 800-square-foot facility on Parkland Drive in Rockville, has since moved to a larger space and now employs about 40 people who work on the development of a vaccine using weakened malaria sporozoites (the first stage in the life cycle of the parasite). Painstakingly extracted from the salivary glands of irradiated mosquitoes, the sporozoites are purified, placed in a vial and frozen in the vapor phase of liquid nitrogen.
The vaccine was tested in a 2009 trial that administered the drug subcutaneously (under the skin) and intradermally (within the skin). Only two of 80 volunteers received protection against the disease. But Hoffman, now in his 60s, was certain that the trial I enrolled in would be different. Human volunteers were to be injected intravenously, so the irradiated sporozoites would go directly into the bloodstream and have a greater chance of reaching the liver.
“It’s been known for many years that sporozoites could deliver high-level protection against malaria, but no one thought it was possible to actually manufacture such a vaccine,” Hoffman would later tell me. “…And here we are now with tremendous success, and we believe that we actually have a tool that can be used to eliminate malaria from defined areas very soon.”
In 2011, 887 people were prescreened for the trial at the NIH Vaccine Research Center. Only 57 were chosen to participate. I was one of them.
In the weeks that followed, I heard horror stories from my parents about vaccine studies gone wrong and watched friends back away, fearful I’d somehow transmit the disease. Some considered me crazy; others figured I must be really strapped for cash. I ignored them all.
My NIH visits began early in 2012. Every few weeks I dragged myself to the clinic to have my blood drawn while scientists asked about my medical history and made me promise not to travel to Africa—at least while taking part in the trial.
“You have amazing veins,” the nurses told me as they gazed enthusiastically at my forearm and eagerly pricked me with needles. I had never before viewed my bulging veins as a source of pride.
In July 2012, after an initial screening qualified me as a “healthy volunteer,” I received my first of four injections, which each consisted of 135,000 irradiated sporozoites and were administered at three-week intervals. For seven days after each vaccination, I was instructed to fill out diary cards, recording my body temperature and any symptoms. Aside from unusually vivid dreams and my typical stress-induced headaches, I never noticed anything abnormal. I had no fear of needles, blood, IVs, or vaccines, and the visits seemed no more worrisome than a regular doctor’s appointment.
