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Journal of Virology, December 1998, p. 9567-9574, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Immunization with a Single Major Histocompatibility
Complex Class I-Restricted Cytotoxic T-Lymphocyte Recognition
Epitope of Herpes Simplex Virus Type 2 Confers Protective
Immunity
Joseph E.
Blaney Jr.,1
Eri
Nobusawa,2,
Michael A.
Brehm,1
Robert H.
Bonneau,1
Lawrence M.
Mylin,1
Tong-Ming
Fu,1,
Yoshihiro
Kawaoka,2 and
Satvir S.
Tevethia1,*
Department of Microbiology and Immunology,
The Pennsylvania State University College of Medicine, Hershey,
Pennsylvania 17033,1 and
Department of
Pathobiological Sciences, University of Wisconsin, Madison,
Wisconsin 537062
Received 27 May 1998/Accepted 25 August 1998
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.
*
Corresponding author. Department of Microbiology and
Immunology, The Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033. Phone: (717) 531-8872. Fax: (717)
531-6522. E-mail: sst1{at}psu.edu.

Present address: Department of Virology, Nagoya City University
Medical School, Mizuho-ku, Mizuho-cho, Nagoya,
Japan.

Present address: Department of Virus and Cell Biology, Merck
Research Laboratories, West Point, PA
19486.
Journal of Virology, December 1998, p. 9567-9574, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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