Risk of Zika Microcephaly May Depend on Features of Maternal Antibodies

By Megan Brooks

August 16, 2019

NEW YORK (Reuters Health) - The risk of Zika-associated microcephaly may depend on the features of antibodies produced by pregnant mothers in response to Zika infection, a finding that has implications for vaccine development, researchers say.

"Our results support the hypothesis that an antibody-mediated mechanism may be associated with the development of Zika brain damage and microcephaly. Therefore, vaccine development could be problematic. A safe vaccine would need to induce antibodies that are protective and avoid those with the potential to increase the risk of microcephaly," Dr. Davide Robbiani from The Rockefeller University in New York City told Reuters Health by email.

Microcephaly occurs in about 5% of babies born to mothers with Zika virus infection. "Why some Zika virus-infected pregnant women deliver apparently healthy newborns while others have babies with microcephaly is unknown," Dr. Robbiani and colleagues explain in the Journal of Experimental Medicine, online August 14.

They examined maternal sera samples collected at the time of delivery from 160 Zika-infected mothers in Brazil between 2015 and 2016 during the period of the Zika-linked microcephaly outbreak. They had 43 samples from mothers of babies with microcephaly and 117 from mothers of apparently healthy babies.

Extensive laboratory testing showed no marked differences between mothers of microcephalic babies and those of healthy babies in the activity of antibodies against dengue or other Zika-related viruses, suggesting that prior exposure to these viruses does not increase the risk of Zika-associated microcephaly, the researchers report.

However, mothers with an intermediate or higher Zika virus antibody enhancement titer (that is, the specific concentration of antibodies that most efficiently enhances infection) were at increased risk of delivering a baby with microcephaly, relative to mothers with lower titers (P<0.0001).

Zika antibodies in mothers of microcephalic babies were more effective at neutralizing the virus than Zika antibodies produced by mothers of healthy newborns. However, these antibodies also showed an enhanced ability to boost the entry of Zika virus into cultured cells, the researchers say.

An analysis of Zika virus-infected pregnant monkeys also found that fetal brain damage was more common in mothers with higher enhancement titers.

The study suggests that features of the maternal antibodies are associated with and may contribute to the development of Zika virus-associated microcephaly, the researchers say.

"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," Dr. Robbiani added in a news release.

The study had no commercial funding.

SOURCE: http://bit.ly/2TCY3Lu

J Exp Med 2019.