Chasing the Dream: The World’s Most Powerful Malaria Vaccine

“It was a landmark study,” says Irwin Sherman, a professor emeritus of biology at the University of California, Riverside, who has studied malaria for a half-century. “It was extremely brave of them to attempt the human trial.”

Sherman, who went to college with Vanderberg in the 1950s, is the author of “The Elusive Malaria Vaccine: Miracle or Mirage?” published in May by ASM Press. He says that, although the experiment at the now-defunct prison was a great leap forward, some researchers were unimpressed by the protection of only one in three people. But, he counters, “the fact of the matter is that some people were actually protected.” Had the first few experiments been 100 percent successful, they would have been “too good to be true and probably suspect.”

Video: Inside the lab, NYU researchers hunt for an effective malaria vaccine.

After the experiment was done, Vanderberg returned to New York. “They needed me to dream up the idea and show that it could be done,” he says about his fellow malaria researchers at the prison. “When they recognized how simple it was, they didn’t need me anymore.”

But Vanderberg continued his studies in mice. Although nobody fully understands how the sporozoite vaccine works, recent work in Vanderberg’s lab gives some clues. In a paper published this April in PLoS Pathogens, the researchers found that as soon as the mosquito dips its proboscis into the skin of an immunized mouse, the body kicks off an aggressive counterattack. Immediately, heaps of small antibodies lock on to the proboscis tip, where they clog the flow of saliva and sporozoites. “It’s like trying to blow through a straw that someone blocked,” Vanderberg says. For the sporozoites that manage to squeeze through the congestion, more antibodies and belligerent immune cells await in the skin. Within a minute or two of molecular battle, the parasites stop dead in their wriggly tracks. After a few hours only scattered bits and pieces of them remain to be cleared away by scavenger cells. The mouse is as healthy as ever.

Enticing as the vaccine may seem, the delivery method that Vanderberg came up with was hugely impractical, and the researchers never believed it could be used in the field. “We weren’t going to cure malaria by irradiated mosquitoes feeding on large numbers of people,” Vanderberg says. “It was just not going to happen.”

In addition, the experimentation at the prison had started to cause unrest among the inmates shortly after Vanderberg left. The outside world grew concerned, and the American Civil Liberties Union filed a lawsuit. The ACLU lost the case, but in the end the research program was shut down anyway. And with that, the human sporozoite vaccine was pretty much left to the crumbling pages of a medical journal.

Enter Dr. Stephen Hoffman. As head of the malaria program at the U.S. Naval Medical Research Center in the 1980s and ’90s, he had turned to the brave new world of molecular biology to skirt the practical headaches of a vaccine based on whole sporozoites. Researchers in Hoffman’s lab and elsewhere now sought to trigger immunity with only a small part of a protein from the parasite’s surface instead of using the entire organism. The vaccine could be produced easily in the lab and injected directly into the bloodstream with a normal syringe. But despite the promise, Hoffman — like the rest of the world — failed to come up with anything near the protection that normal vaccines provide: at or above 90 percent.

Inspired by Vanderberg’s findings, Hoffman had also immunized a dozen people (including himself) with irradiated mosquitoes over the years. But he had never analyzed all the results together. When he finally did, in 2000, he almost couldn’t believe what he found. “I looked at it to my astonishment and horror and said, ‘My God, if I had been working on this, we probably would have a malaria vaccine already.’”

In 2002, Hoffman presented his results to 150 scientists at a meeting in Colorado entitled “Malaria’s Challenge: From Infants to Genomics to Vaccines.” He showed that the sporozoite vaccine, delivered by mosquitoes, protected 10 out of 11 volunteers from getting malaria when bitten. And then he suggested making it into a large-scale vaccine. “You could hear a pin drop,” he says. “Not one person thought that I was anything other than completely whacked-out.”

Andrew Read, who was present at the meeting, describes his reaction as “shock that after all the promises by the molecular guys, one of the stars was reduced to advocating such a low-tech, brute-force approach.” Now a professor of biology and entomology at The Pennsylvania State University, Read recalls in an email that “I left the meeting skeptical that lack of money was the reason we hadn’t got a vaccine, as many at the meeting argued.”

That same year, Hoffman resigned from his job to dedicate himself entirely to revamping the sporozoite vaccine. In his kitchen he laid out a business plan with his son, a recent college graduate who had just returned from surfing and sailing in Hawaii. He called his company Sanaria and launched it in a strip mall in Rockville, Md.