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July 31, 2017

Discovery of a Zika antibody Offers Hope for A Vaccine
By Wynne Parry

A recent study from the laboratories of Dr. Michel Nussenzweig and Dr. Charles Rice found neutralizing antibodies to the Zika virus in blood samples from subjects in Mexico and Brazil. The antibodies appeared to have been initially generated in response to an earlier infection by a related virus that causes dengue.

“In the near future, these antibodies could be very useful. One could envision, for example, administering them to safely prevent Zika among pregnant women or others at risk of contracting the disease,” says Davide F. Robbiani, a research associate professor in the Nussenzweig lab. He and Leonia Bozzacco, a research affiliate in Rice lab, led the study, which appeared in Cell in May.

The team’s detailed examination of the interaction between this antibody and the virus also revealed a new potential strategy for developing a vaccine. A mosquito-borne virus, Zika usually causes mild symptoms in those who contract it. However, dramatic effects can appear in the next generation. Babies born to women infected during pregnancy are at risk of devastating neurodevelopmental abnormalities. The only way to prevent Zika is to avoid mosquito bites; there are currently no vaccines or other medical measures.

Through collaborators working in Pau da Lima, Brazil, and Santa Maria Mixtequilla, Mexico, they obtained blood samples from more than 400 people, collected shortly after Zika was circulating. Individual responses to the same pathogen can vary greatly. Yet a deeper analysis of samples from six of the volunteers with the most promising antibodies revealed a surprise: five of them contained nearly identical antibodies. When the team examined these closely related antibodies’ performance against Zika, one, obtained from a Mexican volunteer’s blood, stood out. When this antibody, called Z004, was given to mice rendered vulnerable to Zika, it protected them from developing serious infections.

An infection begins when the virus, traveling in a spherical particle studded with the viral envelope protein, latches onto a host cell and gains entry into the cell. Faced with a viral threat, the human immune system generates antibodies that recognize the virus and stop it from invading cells. The team set out to find antibodies tuned to a particular target: a part of Zikas envelope protein that the virus needs to infect cells.

To get a closer look at the interaction between the antibody and a fragment of the virus’ envelope protein, scientists in Pamela J. Bjorkman’s lab at Caltech determined the molecular structure formed as the two units interacted. The structure identified a ridge on the viral protein to which the antibody attaches. While some efforts to develop a vaccine use all or most of the virus to stimulate the immune system, the researchers believe it could be safer to employ only a tiny fragment containing this ridge.

Zika isn’t the only virus with this ridge, as it is also present in the envelope proteins of other viruses in the same family. The dengue 1 virus, a close relative of Zika and one of four types of dengue, has a similar ridge and the Z004 antibody neutralized this virus as well.

A look back at samples from the Brazilians, collected six months before Zika arrived by a team led by Albert Ko of Yale University, revealed evidence of prior dengue 1 infections in some—and a potential explanation as to why certain people’s immune systems fared better against Zika. “Even before Zika, their blood samples likely had antibodies that could interact with this same spot on the envelope protein,” says Margaret R. MacDonald, a research associate professor in Rice’s lab. “It appears that, much like a vaccine, dengue 1 can prime the immune system to respond to Zika.”