Malaria and Monogamy

But the Nussenzweigs were just getting warmed up. They left Brazil in 1964 because “it became impossible to work” at the university under military rule, Victor recalls without elaborating. Malaria was waiting for them in New York City.

After they began collaborating on malaria, T. cruzi would seem like a distant memory. Ruth admits that the Chagas’ disease parasite is still her second favorite protozoan. Victor will not even enter the discussion. “No second favorites!” he declares. “We’re monogamous.”

The Secret Is on the Surface

Although it was impractical, Ruth Nussenzweig and Vanderberg’s early work with the malaria parasite showed that something must have been working. The research at New York University moved to developing a vaccine made from just one part of the parasite, called a subunit vaccine.

When Ruth and her team incubated blood from mice during the early, sporozoite stage of infection, they saw something moving on the surface of the parasite. “Something sloughed off,” Victor says.

Ruth easily convinced Victor that there was something important in whatever came off the surface. Victor, who had been working on other diseases, jumped into the work.

They found that antibodies were responding to one of the proteins on the surface, known as the circumsporozoite, or CS, protein. Without that surface protein, the parasite was neutralized and did not cause infection. By only working with the one protein, instead of the entire protozoan, there was no way for the vaccine to cause malaria.

The New York University team proved it was the CS protein that sparked the immune response. They also stopped the parasite from embedding in liver cells, where even a single protozoan would produce thousands more.

After the Nussenzweigs discovered how to keep the parasite from multiplying in the body and infecting red blood cells, the search for a malaria vaccine was on. “There was a big brouhaha in the press,” Victor says. Nearly everyone assumed the problem of malaria had been solved. The year was 1982.

The Distant Finish Line

Ruth’s success in the field brought her to conferences all over the planet, often in Thailand or Africa, where malaria has hit hardest. Victor is still bitter that she racked up all those miles before frequent flyer programs. “She had more miles than Kissinger,” he says.

After the Nussenzweigs proved that the CS protein triggered the immune system, the race was on between the New York University researchers and those at Walter Reed Army Institute of Research in Silver Spring, Md. A young Steven Hoffman, who is now the CEO of Sanaria, was part of the Walter Reed team.

The Nussenzweigs joined with the Swiss pharmaceutical giant Hoffmann-La Roche, while Walter Reed aligned with what is now GlaxoSmithKline. The competing groups simultaneously cloned the gene that makes the CS surface protein in 1984. Ruth was made chair of the newly established Department of Medical and Molecular Parasitology at New York University, and it seemed as though a vaccine was imminent.

But there was nothing simple about getting high levels of protection in humans. Any adjustment meant starting from scratch.

“It’s not like going to the moon,” Victor says. The National Aeronautics and Space Administration might disagree with Victor Nussenzweig about the ease of space travel, but they put a man on the moon in ten years. It has taken more than three decades to even flirt with the idea of an approved malaria vaccine.

After the gene that makes the key surface protein was cloned, the Nussenzweigs’ New York University team synthesized part of that protein and added it into an already successful vaccine—the tetanus toxoid vaccine. The tetanus shot acted as a delivery mechanism for the malaria antibodies, essentially delivering two vaccines in one shot.

Three of the 25 human volunteers who received the vaccine were exposed to malaria-infected mosquitoes to test for immunity. Only one was protected from malaria.

Down at Walter Reed, the U.S. Army was doing things a little differently. They created a vaccine by directly inserting the gene for the CS protein into a virus, instead of synthesizing the protein as the New York University researchers had done. As the virus replicated, the gene would make the malaria antibodies. But only one of six army volunteers was completely protected.

The vaccines from both groups provided some immunity, but not enough. The CS protein was only part of the solution. The nitty-gritty work of creating a vaccine was just getting started.