Birth defects caused by the Zika virus can occur at any point during pregnancy, but scientists now know that the dangers of contracting Zika are especially heightened during the first trimester. A new study suggests that early pregnancy is such a risky time because the virus tricks a pregnant woman’s immune system, making it easier for Zika to spread to the fetus.
“We found that the Asian Zika virus evolved to use the mother’s immune system to infect and ultimately cause congenital disease,” says senior study author Jae Jung, a professor and chair of the department of molecular microbiology and immunology at the Keck School of Medicine of USC. Jung’s study, published in the journal Nature Microbiology, found that the Zika virus targets specific white blood cells that hamper the immune response of pregnant women.
The body's immune system is supposed to attack any foreign invaders, and pregnant women's immune systems are naturally suppressed in order to protect the fetus from that immune response. However, this means that pregnant women are also more susceptible to viruses. In the study, Jung and his team found that Zika takes advantage of the weakened immune system and causes a pregnant woman's immune defense to be even lower than usual.
The researchers took blood samples from 30 healthy people from ages 18 to 39. The samples came from pregnant women, women who weren't pregnant and men. Researchers then infected the blood samples with African and Asian Zika virus (the Asian Zika strain is the one responsible for the most recent outbreak) and compared their findings to blood samples from five healthy pregnant women and 30 Zika-positive pregnant women.
When the researchers looked specifically at the infected blood of pregnant and non-pregnant women, they found that the virus targeted specific white blood cells that turned into large white blood cells called macrophages, which engulf and clear out cell debris.
The researchers found that the Asian Zika virus strain caused the macrophages to become “M2 macrophages,” which are cells that signal that the body is healing and turn off immune system activation. Jung says that by tricking the immune system into thinking that the infection is healing, the Zika virus is allowed to continue spreading and replicating. Prior research shows that Zika can replicate itself thousands of times in the placenta of pregnant women and in the brains of fetuses.
Pregnant women naturally have higher levels of M2 macrophages, and the researchers found that the Asian Zika virus substantially increased M2 macrophages production and lowered the number of infection-fighting cells in the blood of pregnant women. The African Zika virus caused similar increases in M2 macrophages, but the Asian strain caused significantly more. Women who weren't pregnant also experienced a suppressed immune system from the virus, but the effect was much stronger in pregnant women.
Overall, the Asian Zika virus increased immune system suppression by about 70% the study authors say.
So far, about 3,000 cases of microcephaly in infants have come from mothers who were infected before they gave birth. Jung and his team argue that the Zika vaccine needs to be tested in pregnant women in order to confidently know if it can be protective. Currently, clinical trials of the Zika vaccine do not include pregnant women. "Over 90% of vaccine trials and drug development clinical trials do not include pregnant women because they are a vulnerable population," says Jung. "On the other hand, the Zika vaccine is primarily for pregnant women."
Jung says that since his trial shows that a pregnant woman's immune system is different from a non-pregnant woman's, the effectiveness of a vaccine could be different, so pregnant women should be included in testing.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which is supporting vaccine trials, says that in the future they may test the vaccine in pregnant women, but that there are scientific and ethical reasons for why it must first be tested in healthy non-pregnant people. "One of the most important realities of vaccine testing is that you want to do no harm, because you are giving it to people that are well," says Fauci. "You don't want to give it to a pregnant woman or fetus until you know that's safe and effective in a large number of non-pregnant people."