Zika-Associated Birth Defects May Depend on Maternal Immunity

New research led by scientists at The Rockefeller University in New York may help explain why Zika virus infection causes birth defects in some children but not others. The study, which was published today in Journal of Experimental Medicine, suggests that the risk of developing microcephaly depends on the types of antibodies produced by pregnant mothers in response to Zika infection.

The Zika virus is spread by mosquitoes in tropical and subtropical regions, and, in most adults, the symptoms of infection are fairly mild. But the widespread Zika outbreak in Brazil in 2015–2016 revealed that infection during pregnancy can cause a wide range of fetal abnormalities, with microcephaly occurring in around 5% of live births by Zika-infected mothers.

“Why some Zika virus–infected pregnant women deliver apparently healthy newborns while others have babies with microcephaly is unknown,” says first author Davide F. Robbiani.

Robbiani and colleagues analyzed blood samples collected during the 2015–2016 outbreak from Zika-infected mothers who gave birth to either healthy or microcephalic children. Through a series of laboratory tests, the researchers saw no significant differences in the activity of antibodies produced against dengue or other Zika-related viruses, suggesting that prior exposure to these viruses does not increase the risk of Zika-associated birth defects.

However, when Robbiani and colleagues analyzed the activity of antibodies produced against the Zika virus itself, they saw several differences in the antibodies produced by the mothers of babies with microcephaly. Antibodies from these mothers were actually more effective at neutralizing the Zika virus than the antibodies produced by mothers of healthy newborns. Surprisingly, however, these antibodies also showed an enhanced ability to boost the entry of Zika virus into human cells grown in the laboratory. The researchers confirmed their findings in macaques infected with the Zika virus.

“Though our results only show a correlation at this point, they suggest that antibodies may be implicated in Zika fetal disease,” Robbiani says. “Antibodies may exist that, instead of protecting, enhance the risk of Zika microcephaly, so the next step will be to figure out which antibodies are responsible for this, and how they promote fetal damage.”