It makes sense that scientists would focus on dengue as a way to better understand Zika. Both are in the same family of viruses, and understanding cross-reactivity among related viruses is a cornerstone of vaccination. This kind of research “was the immunological basis for the first human vaccine against smallpox introduced more than 200 years ago,” according to a 2012 paper in the Expert Review of Vaccines, “and continues to underpin modern vaccine development.”
Now, researchers have identified two antibodies, generated by people who have been infected with dengue, that can bind to the Zika virus and prevent an infection. In their paper, published in Nature on Thursday, they describe the importance of studying the structures of those antibodies as a way to design a vaccine that protects against Zika. And although researchers knew going-in that Zika and dengue are both flaviviruses, the antibody response was a surprise.
“We did not indeed expect that neutralizing antibodies generated after dengue infection could be even more potent in neutralizing Zika virus,” Giovanna Barba Spaeth, one of the paper’s authors, told me. The finding has major implications for protection against both Zika and dengue, since the antibodies target the same region on both viruses. “It suggests that a vaccine including this region would generate protection against both viruses,” she said.
But the path to developing a vaccine isn’t exactly straightforward.
In a related paper, published in Nature Immunology, researchers found that antibodies generated by someone who has previously had dengue aren’t always protective. These antibodies can actually enhance Zika’s ability to replicate and thrive. In other words, a previous dengue infection may put someone at higher risk of contracting Zika—even though certain dengue-prompted antibodies could help lead to a Zika vaccine. But in areas where there have been both Zika and dengue outbreaks, it’s difficult to compare the severity of post-dengue Zika with cases in which people have only contracted Zika. “Most of the people who have had Zika have been previously infected with dengue,” said Gavin Screaton, one of the authors of the Nature Immunology paper. “After people have had Zika, it is difficult to distinguish those who have had Zika only from those who have had Zika and dengue.”
The mechanism in which the antibodies from one virus enhance the infection of another virus is known as antibody-dependent enhancement, and it’s a feature that has already complicated attempts at developing a vaccine for dengue alone. (Antibody-dependent enhancement also helps explain why secondary dengue infections are often more dangerous to a person than the first time that person comes down with the virus.)
“Given that the prevalence of dengue exceeds 90 percent in some regions affected by Zika,” Nature wrote in a statement about the new research, “these findings could have important implications” for understanding the mechanics of Zika’s spread—understanding which is critical for vaccine development.