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PMID: 9811690 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity.

Journal of virology ·Vol. 72 ·No. 12 ·1998-12-00 ·Pages 9567-74

Blaney JE, Nobusawa E, Brehm MA, Bonneau RH, Mylin LM, Fu TM, Kawaoka Y, Tevethia SS

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.

MeSH Terms
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
Chemicals
Antigens, Viral Epitopes H-2 Antigens H-2Kb protein, mouse Histocompatibility Antigens Class I Viral Envelope Proteins glycoprotein B, herpes simplex virus type 2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Blaney J E
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Nobusawa E
Brehm M A
Bonneau R H
Mylin L M
Fu T M
Kawaoka Y
Tevethia S S
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.12.9567-9574.1998
Published
1998-12-00
Pages
9567-74
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110466
Subset
IM
Grants
NCI NIH HHS · T32 CA060395 · United States
NCI NIH HHS · 5T32CA60395 · United States
NIAID NIH HHS · AI29599 · United States
NIAID NIH HHS · AI34070 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.12.9567-9574.1998 PMC Full Text View journal details
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