Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease.

Yike Jiang,Francesca Gilli,Iara M Backes,Lananh N Nguyen,David A Posner,Brian North,David A Leib,Chaya D Patel,Andrew R Pachner,Richard Manivanh,Anne Moscona

doi:10.1128/mbio.00678-17

Abstract

ABSTRACTWhile antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. In this study on herpes simplex virus 1 (HSV-1), we demonstrate that HSV-specific antibodies are present during HSV-1 latency in the nervous systems of both mice and humans. We show that antibody-secreting cells entered the trigeminal ganglion (TG), a key site of HSV infection, and persisted long after the establishment of latent infection. We also demonstrate the ability of passively administered IgG to enter the TG independently of infection, showing that the naive TG is accessible to antibodies. The translational implication of this finding is that human fetal neural tissue could contain HSV-specific maternally derived antibodies. Exploring this possibility, we observed HSV-specific IgG in HSV DNA-negative human fetal TG, suggesting passive transfer of maternal immunity into the prenatal nervous system. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG. This maternal antibody not only prevented disseminated infection but also completely protected the neonate from neurological disease and death following HSV challenge. Maternal antibodies therefore have a potent protective role in the neonatal nervous system against HSV infection. These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization.

Highlights

While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood
Using mouse and human tissue, we discovered that antiviral antibodies accumulate in neural tissue after herpes simplex virus 1 (HSV-1) infection in adults
herpes simplex virus (HSV) replicates in the cornea and spreads in a retrograde direction along the ciliary nerves into the trigeminal ganglion (TG), where it establishes latency [27, 28]

Summary

Introduction

While antibody responses to neurovirulent pathogens are critical for clearance, the extent to which antibodies access the nervous system to ameliorate infection is poorly understood. To further investigate the role of maternal antibodies in the neonatal nervous system, we established a murine model to demonstrate that maternal IgG can access and persist in neonatal TG This maternal antibody prevented disseminated infection and completely protected the neonate from neurological disease and death following HSV challenge. We found that antiviral maternal antibodies can readily access neural tissue of the fetus and neonate These maternal antibodies protect neonatal mice against HSV-1 neurological infection and death. These results underscore the previously unappreciated role of maternal antibodies in protecting fetal and newborn nervous systems against infection. This work highlights the importance of maternal antibodies in protecting the newborn nervous system from viral infections These findings strongly support the concept that prevention of prenatal and neonatal neurotropic infections can be achieved through maternal immunization

Methods

Results

Conclusion