Neonatal Herpes Simplex Infections
Primary HSV-1 or HSV-2 infection during pregnancy carries a high risk of perinatal transmission and neonatal disease. Neonatal infection during the peripartum period accounts for 85% of cases and 15% are caused during the postnatal period. These neonatal infections manifest as one of three diseases presentations: Disease limited to the skin, disease of the eyes or mouth (SEM disease); primary central nervous system disease, which carries the highest rate of morbidity in these infants; and disseminated disease, which has the highest mortality rate.
Maternal immunization has been shown to successfully prevent against several diseases in infants. For example, maternal vaccination with inactivated influenza or acellular pertussis partially protects infants because maternal immunoglobulin G (IgG) is transferred across the placenta in a process mediated in part by antibodies (Abs) binding to the neonatal Fc receptor (FcRn) in the placental syncytiotrophoblast. Several factors modulate placental transfer of IgG, including the affinity for the FcRn, total maternal Ab concentration, and infant gestational age. There are limited clinical studies explaining the potential role of FcγRs activating Abs to protect against neonatal herpes disease. A clinical study conducted from the early 1990s evaluating 47 infants with HSV infection concluded that highest levels of ADCC Abs were detected in infants with disease limited to the skin and lowest in those with disseminated disease.
Our overarching hypothesis is that immunization of reproductive aged women with ∆gD-2 vaccine will protect neonates from perinatal acquisition of herpes and may be effective in both seronegative and seropositive women because it elicits (seronegative) and boosts (seropositive) ADCK Abs that cross the placenta. The vaccine is currently in preclinical development. As a first step in planning for potential future clinical studies, we propose to conduct a pospective cohort study to quantify the placental transfer of total and viral specific (acquired in response to natural infection) maternal antibodies as well as the functionality of neonatal immune cells to mediate antibody dependent killing (ADCK).