Maternal immunization with a herpes simplex virus type 2 replication-defective virus reduces visceral dissemination but not lethal encephalitis in newborn mice after oral challenge.

Abstract

Herpes simplex virus (HSV) causes devastating infections in newborns. Maternal immunization is one potential strategy to reduce neonatal HSV disease. Female mice were immunized with an HSV type 2 (HSV-2) replication-defective mutant (HSV-2 dl5-29, which is defective for the genes UL5 and UL29) and then mated. Protection was evaluated in newborn mice after a virulent HSV-2 oral challenge. Heightened neonatal susceptibility was observed to a thymidine kinase-negative HSV-2 strain (HSV-2 186DeltaKpn) that is highly attenuated in adult mice. Maternal immunization with HSV-2 dl5-29 and HSV-2 186DeltaKpn reduced visceral spread of infectious challenge virus in pups after challenge at either 1 day or 1 week of age but did not prevent replication at the site of entry, spread to the central nervous system, or lethal encephalitis. No protection was seen in pups born to mock-immunized mothers or to mothers immunized with a UV-inactivated wild-type HSV-2 strain. Levels of protection correlated with levels of passively transferred maternal HSV-2-specific IgG antibody.