|
| Article Authors: | J E Blaney Jr; E Nobusawa; M A Brehm; R H Bonneau; L M Mylin; T M Fu; Y Kawaoka; S S Tevethia |
|---|
| Article 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. |
|---|
|
| Reference ID: | 1485 |
|---|
| 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. |
|---|
| Affiliations: | Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. |
|---|
| Date: | 1998 |
|---|
| Reference Type: | Literature |
|---|
| PubMed ID: | 9811690 |
|---|
| Journal: | J Virol |
|---|
| Journal Volume: | 72 |
|---|
| Article Pages: | 9567-74 |
|---|
| Journal ISSN: | 1098-5514 |
|---|
| Article Chemical List: | Antigens, Viral;Epitopes;H-2 Antigens;H-2Kb protein, mouse;Histocompatibility Antigens Class I;Viral Envelope Proteins;glycoprotein B, herpes simplex virus type 2 |
|---|
| Article MeSH List: | Amino Acid Sequence; Animals; Antigens, Viral(genetics); Central Nervous System(immunology; virology); Epitopes(genetics); H-2 Antigens; Herpes Genitalis(immunology; prevention & control; virology); Herpesvirus 2, Human(genetics; immunology; isolation & purification); Histocompatibility Antigens Class I; Immunity, Mucosal; Immunization; Immunologic Memory; Male; Mice; Mice, Inbred C57BL; Recombination, Genetic; T-Lymphocytes, Cytotoxic(immunology); Vaccinia virus(genetics); Viral Envelope Proteins(genetics; immunology) |
|---|
| Curation Last Updated: | 2013-05-28 20:07:36 |
|---|