title: Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity.
abstract: We have evaluated the potential of conferring protective immunity to herpes simplex virus type 2 (HSV-2) by selectively inducing an HSV-specific CD8(+) cytotoxic T-lymphocyte (CTL) response directed against a single major histocompatibility complex class I-restricted CTL recognition epitope. We generated a recombinant vaccinia virus (rVV-ES-gB498-505) which expresses the H-2Kb-restricted, HSV-1/2-cross-reactive CTL recognition epitope, HSV glycoprotein B residues 498 to 505 (SSIEFARL) (gB498-505), fused to the adenovirus type 5 E3/19K endoplasmic reticulum insertion sequence (ES). Mucosal immunization of C57BL/6 mice with this recombinant vaccinia virus induced both a primary CTL response in the draining lymph nodes and a splenic memory CTL response directed against HSV gB498-505. To determine the ability of the gB498-505-specific memory CTL response to provide protection from HSV infection, immunized mice were challenged with a lethal dose of HSV-2 strain 186 by the intranasal (i.n.) route. Development of the gB498-505-specific CTL response conferred resistance in 60 to 75% of mice challenged with a lethal dose of HSV-2 and significantly reduced the levels of infectious virus in the brains and trigeminal ganglia of challenged mice. Finally, i.n. immunization of C57BL/6 mice with either a recombinant influenza virus or a recombinant vaccinia virus expressing HSV gB498-505 without the ES was also demonstrated to induce an HSV-specific CTL response and provide protection from HSV infection. This finding confirms that the induction of an HSV-specific CTL response directed against a single epitope is sufficient for conferring protective immunity to HSV. Our findings support the role of CD8(+) T cells in the control of HSV infection of the central nervous system and suggest the potential importance of eliciting HSV-specific mucosal CD8(+) CTL in HSV vaccine design.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Blaney
authors.forename: E
authors.initials: E
authors.lastname: Nobusawa
authors.forename: M A
authors.initials: MA
authors.lastname: Brehm
authors.forename: R H
authors.initials: RH
authors.lastname: Bonneau
authors.forename: L M
authors.initials: LM
authors.lastname: Mylin
authors.forename: T M
authors.initials: TM
authors.lastname: Fu
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: S S
authors.initials: SS
authors.lastname: Tevethia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D002490:Central Nervous System / Q000276:immunology / Q000821:virology; D000939:Epitopes / Q000235:genetics; D006183:H-2 Antigens; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I; D018928:Immunity, Mucosal; D007114:Immunization; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D014759:Viral Envelope Proteins; C044525:glycoprotein B, herpes simplex virus type 2