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Sci Transl Med. 2019 Apr 10;11(487). pii: eaau6039. doi: 10.1126/scitranslmed.aau6039.

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

Author information

1
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
2
Guarini School of Graduate and Advanced Studies at Dartmouth, Hanover, NH 03755, USA.
3
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
4
Institute for Medical Immunology, Université libre de Bruxelles, Charleroi B-6041, Belgium.
5
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
7
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA. david.a.leib@dartmouth.edu.

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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