title: Immunization with a highly attenuated replication-competent herpes simplex virus type 1 mutant, HF10, protects mice from genital disease caused by herpes simplex virus type 2.
abstract: Genital herpes is an intractable disease caused mainly by herpes simplex virus (HSV) type 2 (HSV-2), and is a major concern in public health. A previous infection with HSV type 1 (HSV-1) enhances protection against primary HSV-2 infection to some extent. In this study, we evaluated the ability of HF10, a naturally occurring replication-competent HSV-1 mutant, to protect against genital infection in mice caused by HSV-2. Subcutaneous inoculation of HF10-immunized mice against lethal infection by HSV-2, and attenuated the development of genital ulcer diseases. Immunization with HF10 inhibited HSV-2 replication in the mouse vagina, reduced local inflammation, controlled emergence of neurological dysfunctions of HSV-2 infection, and increased survival. In HF10-immunized mice, we observed rapid and increased production of interferon-γ in the vagina in response to HSV-2 infection, and numerous CD4(+) and a few CD8(+) T cells localized to the infective focus. CD4(+) T cells invaded the mucosal subepithelial lamina propria. Thus, the protective effect of HF10 was related to induction of cellular immunity, mediated primarily by Th1 CD4(+) cells. These data indicate that the live attenuated HSV-1 mutant strain HF10 is a promising candidate antigen for a vaccine against genital herpes caused by HSV-2.
authors.affiliation: Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Chenhong
authors.initials: C
authors.lastname: Luo
authors.forename: Fumi
authors.initials: F
authors.lastname: Goshima
authors.forename: Maki
authors.initials: M
authors.lastname: Kamakura
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Mutoh
authors.forename: Seiko
authors.initials: S
authors.lastname: Iwata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nishiyama