Severe birth defects caused by the Zika virus may be related to the kinds of antibodies infected mothers produce to fight the disease, a study by YSPH researchers and others shows.
One of the devastating effects of the Zika virus is that it can cause severe birth defects such as microcephaly – a condition in which the head is underdeveloped – in children of pregnant women who are infected.
But not all infected mothers experience such birth outcomes. In fact, less than 10 % of newborn infants born during a 2015 Zika outbreak in Brazil developed severe birth defects due to Zika infection during gestation, according to data collected by researchers at the Yale School of Public Health (YSPH).
Why only some births are impacted by maternal Zika infection and others are not has remained a mystery.
Now, a team of scientists including researchers with the Yale School of Public Health, Oswaldo Cruz Foundation (Fiocruz), the Federal University of Bahia and The Rockefeller University of New York say the reason for this difference might reside in the mother’s antibodies.
In a study reported in the Journal of Experimental Medicine, the researchers show that the risk of giving birth to a child with microcephaly might be related to how the mother’s immune system reacts against the virus—specifically what kind of antibodies it produces.
It’s an insight that might yield important ramifications for ongoing efforts to develop a Zika vaccine.
Clinical Response Provides Critical Data
When the Zika microcephaly outbreak was first identified in the city of Salvador, Brazil at the end of 2015, Albert Ko, professor and chair of Epidemiology of Microbial Diseases at YSPH, Federico Costa, associate professor at the Federal University of Bahia and associate professor adjunct at YSPH, and their colleagues mounted an on-site response.
Together, the researchers established multidisciplinary teams of physicians, nurses and laboratory staff to provide care for infants with birth defects during the outbreak. They also designed a study that recruited mothers and their newborn infants at the city’s largest maternity hospital to understand how Zika causes birth defects.
The clinical results found that approximately 10% of the newborn infants born during the outbreak at the hospital had developed severe birth defects, including microcephaly. This gave rise to a new study exploring potential explanations for the different birth outcomes.
The study analyzed blood samples from 150 pregnant women infected by Zika. The results showed that some of the antibodies mothers were generating to fight Zika infection were possible culprits contributing to the birth defects.
In mothers who delivered babies with microcephaly, the researchers found Zika-specific antibodies possessing molecular features that seemed to correlate with congenital abnormalities. This finding was later confirmed in animals suggesting that, rather than protecting the body from Zika, some antibodies may in fact help the virus enter maternal cells, increasing the risk of fetal brain damage.
“Infection of the mother with the Zika virus produces antibodies that protect the mother and fetus against the virus,” Ko said. “However, our findings suggest that in some mothers, the infection may also produce deleterious antibodies that may increase the risk for infection and birth defects in the fetus.”
There is currently no approved vaccine against Zika and, in light of the new findings, developing one could turn out to be trickier than experts have previously realized.
“Although our results only show a correlation at this point, there could be significant implications for vaccine development,” said Rockefeller Research Associate Professor Davide Robbiani, who led the latest study with Rockefeller colleague Professor Michel Nussenzweig. “A safe vaccine would need to induce the immune system to selectively produce antibodies that are protective, avoiding those that potentially enhance the risk of microcephaly. “
Our findings suggest that in some mothers, the Zika infection may produce deleterious antibodies that may increase the risk for infection and birth defects.
As a first step toward this goal, the team is conducting further research to establish which types of antibodies might be harmful to unborn babies, and by what mechanisms they promote fetal damage.
Yale School of Medicine