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- Title
Murine Model of Maternal Immunization Demonstrates Protective Role for Antibodies That Mediate Antibody-Dependent Cellular Cytotoxicity in Protecting Neonates From Herpes Simplex Virus Type 1 and Type 2.
- Authors
Kao, Carol M; Goymer, Jessica; Loh, Lip Nam; Mahant, Aakash; Aschner, Clare Burn; Herold, Betsy C; Burn Aschner, Clare
- Abstract
<bold>Background: </bold>Neonatal herpes simplex virus (HSV) disease results in unacceptable morbidity and mortality. The primary humoral immune response to natural infection is neutralizing antibodies (Abs). However, Abs that activate Fc gama receptors (FcγRs) and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) may play a dominant role in protection. In adult mice, a single-cycle HSV candidate vaccine deleted in glycoprotein-D (ΔgD-2) that induces ADCC provided complete protection against HSV disease and prevented the establishment of latency. Passive transfer studies showed that Abs were sufficient for protection. The current study tested the hypothesis that maternal immunization with ΔgD-2 would protect neonates.<bold>Methods: </bold>C57BL/6 female mice were vaccinated 3 weeks apart with ΔgD-2, and pups were challenged at different times postnatally with lethal doses of HSV-1 or HSV-2. Concentration and functionality of Abs and immune cells were assessed.<bold>Results: </bold>Maternal ΔgD-2 immunization provided significant protection and reduced viral dissemination after lethal challenge with HSV-1 or HSV-2. Protection correlated with Abs acquired transplacentally or from breastmilk that mediated ADCC. Protection was reduced when pups were challenged on Day 1 of life, and this was associated with decreased ability of newborn cells to mediate Ab-dependent cell killing.<bold>Conclusions: </bold>Antibodies mediating ADCC provide significant protection against neonatal HSV.
- Subjects
MATERNALLY acquired immunity; ANTIBODY-dependent cell cytotoxicity; HUMAN herpesvirus 1; HUMORAL immunity; IMMUNIZATION; HERPES simplex virus; PREVENTION of communicable diseases; HERPES simplex prevention; BIOLOGICAL models; ANIMAL populations; RESEARCH; VIRAL vaccines; IMMUNOGLOBULINS; COMMUNICABLE diseases; ANIMAL experimentation; RESEARCH methodology; HERPES simplex; CELL receptors; EVALUATION research; MEDICAL cooperation; COMPARATIVE studies; IMMUNITY; PREGNANCY complications; RESEARCH funding; HERPESVIRUSES; VIRAL antibodies; MICE
- Publication
Journal of Infectious Diseases, 2020, Vol 221, Issue 5, p729
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiz521