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

被引:101
作者
Blaney, JE
Nobusawa, E
Brehm, MA
Bonneau, RH
Mylin, LM
Fu, TM
Kawaoka, Y
Tevethia, SS
机构
[1] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA
[2] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA
关键词
D O I
10.1128/JVI.72.12.9567-9574.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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-2K(b)-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.
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收藏
页码:9567 / 9574
页数:8
相关论文
共 76 条
[1]   ENDOGENOUSLY SYNTHESIZED PEPTIDE WITH AN ENDOPLASMIC-RETICULUM SIGNAL SEQUENCE SENSITIZES ANTIGEN PROCESSING MUTANT-CELLS TO CLASS-I-RESTRICTED CELL-MEDIATED LYSIS [J].
ANDERSON, K ;
CRESSWELL, P ;
GAMMON, M ;
HERMES, J ;
WILLIAMSON, A ;
ZWEERINK, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (02) :489-492
[2]  
ANDERSON KS, 1993, J IMMUNOL, V151, P3407
[3]   RECOGNITION BY AND INVITRO INDUCTION OF CYTOTOXIC LYMPHOCYTES-T AGAINST PREDICTED EPITOPES OF THE IMMEDIATE-EARLY PROTEIN-ICP27 OF HERPES-SIMPLEX VIRUS [J].
BANKS, TA ;
NAIR, S ;
ROUSE, BT .
JOURNAL OF VIROLOGY, 1993, 67 (01) :613-616
[4]   SPREAD OF HERPES-SIMPLEX VIRUS TO THE CEREBROSPINAL-FLUID AND THE MENINGES IN EXPERIMENTAL MOUSE ENCEPHALITIS [J].
BOERMAN, RH ;
PETERS, ACB ;
BLOEM, BR ;
RAAP, AK ;
VANDERPLOEG, M .
ACTA NEUROPATHOLOGICA, 1992, 83 (03) :300-307
[5]   IN-VIVO PRIMING AND ACTIVATION OF MEMORY CYTOTOXIC T-LYMPHOCYTES (CTL) BY A CHIMERIC SIMIAN VIRUS-40-T ANTIGEN EXPRESSING AN 8 AMINO-ACID RESIDUE HERPES-SIMPLEX VIRUS GB CTL EPITOPE [J].
BONNEAU, RH ;
FU, TM ;
TEVETHIA, SS .
VIROLOGY, 1993, 197 (02) :782-787
[6]   EPITOPE SPECIFICITY OF H-2K(B)-RESTRICTED, HSV-1-CROSS-REACTIVE, AND HSV-2-CROSS-REACTIVE CYTOTOXIC T-LYMPHOCYTE CLONES [J].
BONNEAU, RH ;
SALVUCCI, LA ;
JOHNSON, DC ;
TEVETHIA, SS .
VIROLOGY, 1993, 195 (01) :62-70
[7]   MODULATION OF ACUTE AND LATENT HERPES-SIMPLEX VIRUS-INFECTION IN C57BL/6 MICE BY ADOPTIVE TRANSFER OF IMMUNE LYMPHOCYTES WITH CYTOLYTIC ACTIVITY [J].
BONNEAU, RH ;
JENNINGS, SR .
JOURNAL OF VIROLOGY, 1989, 63 (03) :1480-1484
[8]   HERPES-SIMPLEX VIRUS-SPECIFIC CYTOLYTIC LYMPHOCYTES-T RESTRICTED TO A NORMALLY LOW RESPONDER H-2 ALLELE ARE PROTECTIVE INVIVO [J].
BONNEAU, RH ;
JENNINGS, SR .
VIROLOGY, 1990, 174 (02) :599-604
[9]   Immunization with a replication-deficient mutant of herpes simplex virus type 1 (HSV-1) induces a CD8(+) cytotoxic T-lymphocyte response and confers a level of protection comparable to that of wild-type HSV-1 [J].
Brehm, MA ;
Bonneau, RH ;
Knipe, DM ;
Tevethia, SS .
JOURNAL OF VIROLOGY, 1997, 71 (05) :3534-3544
[10]   THE INFLUENCE OF ADJUVANT ON THE THERAPEUTIC EFFICACY OF A RECOMBINANT GENITAL HERPES VACCINE [J].
BURKE, RL ;
GOLDBECK, C ;
NG, P ;
STANBERRY, L ;
OTT, G ;
VANNEST, G .
JOURNAL OF INFECTIOUS DISEASES, 1994, 170 (05) :1110-1119