B7 costimulation molecules expressed from the herpes simplex virus 2 genome rescue immune induction in B7-deficient mice.
The interaction between B7 costimulation molecules on antigen-presenting cells and CD28 on antigen-responsive T cells is essential for T-cell activation and maturation of immune responses to herpes simplex virus (HSV) infection. Vaccine-induced immune responses also depend upon adequate upregulation of B7 costimulation molecules, but this signal may be limiting for replication-defective virus vaccines. We investigated whether expression of B7 costimulation molecules by a prototypical replication-defective antiviral vaccine could enhance immune responses to the vaccine and whether B7-1 and B7-2 would be similarly effective. We altered an ICP8(-) replication-defective strain of HSV type 2 (HSV-2), 5BlacZ, to encode either murine B7-1 or B7-2. B7 molecule expression was detected on the surface of cells infected in vitro and at the RNA level in tissue of immunized mice. Immunization of B7-1/B7-2 knockout mice with B7-encoding virus modestly expanded the number of gamma interferon-producing T cells and significantly augmented class-switched HSV-specific antibody responses compared with the parental virus. Mice immunized with either B7-expressing virus showed less replication of challenge virus in the genital mucosa than mice immunized with 5BlacZ, markedly fewer signs of genital and neurological disease, and little weight loss. Virtually all mice immunized with B7-encoding virus survived challenge with a large dose of HSV-2, whereas most 5BlacZ-immunized mice succumbed to infection. These results indicate that protective immune responses can be enhanced by the inclusion of host B7 costimulation molecules in a prototypical replication-defective HSV vaccine against HSV-2 genital infection and that B7-1 and B7-2 induce immune responses with similar capacities to fight HSV-2 infection.
Thebeau
Lydia G
LG
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MO 63104, USA.
Vagvala
Sri P
SP
Wong
Yee M
YM
Morrison
Lynda A
LA
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018122:B7-1 Antigen / Q000032:analysis / Q000235:genetics*; D006558:Herpes Genitalis / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D007109:Immunity; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009420:Nervous System / Q000276:immunology / Q000821:virology; D009422:Nervous System Diseases / Q000517:prevention & control* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D014779:Virus Replication