Prenatal Exposure to Respiratory Syncytial Virus Found to Alter Postnatal Immunity

Building on previous findings that maternal-to-fetal transfer of the respiratory syncytial virus (RSV) predisposes babies to airway hyperreactivity, Cleveland Clinic researchers have now confirmed that the virus traverses the placenta, modifying immune response after birth.

“Our results demonstrate that maternal RSV infection alters postnatal offspring immunity, resulting in lower airway lymphocyte and cytokine profiles that are significantly different from that of a RSV-naïve host during a first postnatal RSV lower respiratory tract infection,” says Giovanni Piedimonte, MD, Chairman of Cleveland Clinic Children’s and senior author of the study recently published in PLoS One.

The most significant effects measured after primary early life infection were a sharp increase in CD3+CD4–CD8– T cells, combined with virtual suppression of the production of key Th1-type cytokines like IFN-γ and IL-2; a large increase in the expression of the prototypical neurotrophin NGF; and increased pre- and post-synaptic reactivity of the airways combined with intrinsic hyper contractility of the smooth muscle, delaying its return to resting tone.

“These changes persisted — albeit to a lesser degree — after secondary reinfection and might provide a plausible explanation to the development of chronic airway dysfunction and asthma in a subpopulation of children with history of RSV infections in infancy,” he says.

Suspicions confirmed

Although the Cleveland Clinic studies were performed in rat models, reports of cross-placenta viral transmission in humans have begun to surface.

“The possibility that viruses that give people the common cold can get into the bloodstream, cross the placenta and reach the fetus should not be surprising. I’ve suspected this for several years,” says Dr. Piedimonte. “Look at the Zika virus, which causes kids to be born with microcephaly. It is not bad luck — they are infected with the virus in utero. Indeed, many more congenital abnormalities and chronic health issues may originate from infections acquired in utero.”

Viral infection might have more important consequences when the mother is in the first trimester of pregnancy, prior to development of the fetal immune system. “The immune system develops during the second part of pregnancy by recognizing proteins already present in the fetus. If, during the process, there are proteins that don’t belong, the immune system will still recognize them as self. If the baby is reinfected with the same virus during the first months of life, it will not be able to fight the infection effectively because the immune system has been programmed not to respond,” Dr. Piedimonte explains.

Protecting newborns

These findings underscore the importance of avoiding respiratory infections during early pregnancy. Because this is difficult in most situations, particularly for pregnant women with young children at home, Dr. Piedimonte suggests instituting another layer of protection.

“The same antibody to RSV that we give high-risk infants as prophylaxis could be given to the mothers who are pregnant during the viral season. Even better, the active immunization of pregnant mothers with inactive virus or its components would provide protection to the fetus as well as to the newborn,” he says.

Tip of the iceberg?

Now that the technology to detect infections has become much more sensitive and specific, Dr. Piedimonte expects other vertically transmitted infections to surface as determinants of postnatal diseases.

“I suspect there are more diseases and conditions affecting newborns and evolving in adult life that may be due to situations that occur in pregnancy,” he says. “This adds to the hypothesis that the nine months we are in utero are the most important in determining what will happen medically to us during the rest of our lives.”