Research ArticleInfectious Disease

Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity

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Science Translational Medicine  10 Apr 2019:
Vol. 11, Issue 487, eaau6039
DOI: 10.1126/scitranslmed.aau6039

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Nipping neonatal HSV in the bud

Vertical transmission of herpes simplex virus (HSV) 1 or 2 can have devastating consequences for newborn babies. Despite existing antivirals, systemic HSV can lead to permanent central nervous system damage or even death. Patel et al. examined human samples and used a pregnant mouse model to determine whether maternal immunity could protect against neonatal HSV infection. They detected maternal anti-HSV IgG in cord blood, demonstrating that protective antibodies cross the placenta. Passive transfer of anti-HSV IgG or vaccination of pregnant mice protected pups from neonatal HSV-1 or HSV-2 challenge. Their findings suggest that vaccination of expectant mothers may reduce morbidity and mortality associated with neonatal HSV infections.

Abstract

Neonatal herpes simplex virus (nHSV) infections cause devastating morbidity and mortality in infants. Most nHSV cases are associated with primary maternal infection, consistent with the hypothesis that maternal immunity is protective. In humans, we found HSV-specific neutralizing antibodies in newborns of immune mothers, indicating that placentally transferred HSV-specific antibody is protective. Using a murine model, we showed that passive administration of HSV-specific antibody to dams prevented disseminated infection and mortality in pups. Maternal immunization with an HSV-2 replication-defective vaccine candidate, dl5-29, led to transfer of HSV-specific antibodies into neonatal circulation that protected against nHSV neurological disease and death. Furthermore, we observed considerable anxiety-like behavior in adult mice that had been infected with low doses of HSV as neonates, despite a notable lack of signs of infection. This phenotype suggests that nHSV infection can have an unsuspected and permanent impact on behavior. These behavioral sequelae of nHSV were prevented by maternal immunization with dl5-29, demonstrating an unexpected benefit of immunization. These findings also support the general concept that maternal immunization can prevent neurotropic neonatal infections and associated morbidity and mortality.

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