Skip to main content

Advertisement

Springer Nature Link
Log in

Developments in herpes simplex virus vaccines: Old problems and new challenges

  • Review
  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

Vaccination has remained the best method for preventing virus spread. The herpes simplex virus (HSV) candidate vaccines tested till now were mostly purified subunit vaccines and/or recombinant envelope glycoproteins (such as gB and gD). In many experiments performed in mice, guinea pigs and rabbits, clear-cut protection against acute virus challenge was demonstrated along with the reduction of the extent of latency, when established in the immunized host. The immunotherapeutic effect of herpes vaccines seems less convincing. However, introduction of new adjuvants, which shift the cytokine production of helper T-cells toward stimulation of cytotoxic T-cells (TH1 type cytokine response), reveals a promising development. Mathematical analysis proved that overall prophylactic vaccination of seronegative women, even when eliciting 40–60 % antibody response only, would reduce the frequency of genital herpes within the vaccinated population. Even when partially effective, immunotherapeutic vaccination might represent a suitable alternative of chronic chemotherapy in recurrent labial and genital herpes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

APC:

antigen-presenting cell

CD:

cluster of differentiation

CTL:

cytotoxic T-lymphocyte (TC-lymphocyte)

CNS:

central nervous system

DC:

dendritic cell

E:

early (mRNA expression)

gB, gC, gD, gE, gH:

glycoproteins B-H

HLA:

human leukocyte antigen

HSV:

herpes simplex virus

Hve:

herpes virus entry

i.c.:

intracutaneous

IE:

immediate early

i.m.:

intramuscular

i.n.:

intranasal

ICP:

infected cell protein

IFN:

interferon

IL:

interleukin

LAT:

latency-associated transcript

MHC:

major histocompatibility complex

mRNA:

messenger ribonucleic acid

p.i.:

post-infection

PCR:

polymerase chain reaction

PNS:

peripheral nervous system

PVR:

poliovirus receptor

RT-PCR:

reversed transcription PCR

T-lymphocyte:

thymus-dependent lymphocyte

TCR:

T-cell receptor

TH :

helper T-lymphocyte

TK:

thymidine kinase

TNF:

tumor necrosis factor

UL:

unique long HSV DNA segment

US:

unique short HSV DNA segment

vhs :

virion host shutoff

References

  • Al-Ghandi A., Jennings R., Bentlez H., Potter C.W.: Latent HSV 1 infection in mice immunized with a zwitterionic detergent-extracted HSV 1 antigen preparation.Arch.Virol.108, 19–31 (1989).

    Article  Google Scholar 

  • Altomare G.F., Pigatto P.D., Polenghi M.M., Germogli R.: Relapsed herpes simplex specific immunotherapy with killed virus.Acta Toxicol.Ther.713, 201–210 (1986).

    Google Scholar 

  • Aurelian L.: Herpes simplex virus type 2 vaccines: new ground for optimism?Clin.Diagn.Lab.Immunol.11, 437–445 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Baghian A., Chouljenko V.N., D’Auvergne O., Newman M.J., Baghian S., Kousoulas K.G.: Protective immunity against lethal HSV 1 challenge in mice by nucleic acid-based immunization with herpes simplex virus type 1 genes specifying glycoproteins gB and gD.Virology51, 350–357 (2002).

    CAS  Google Scholar 

  • Balachandran N., Bacchetti S., Rawls W.E.: Protection against lethal challenge of Balb/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2.Infect.Immun.37, 1132–1137 (1982).

    PubMed  CAS  Google Scholar 

  • Baringer J.R.: Herpes simplex virus infection of nervous tissue in animals and man.Progr.Med.Virol.20, 1–26 (1975).

    CAS  Google Scholar 

  • Ben-Mohamed L., Bertrand G., McNamara C.D., Gras-Masse H., Hammer J., Wechsler S.L., Nesburn A.: Identification of novel immunodominant CD4 Th1-type T-cell peptide epitopes from herpes simplex virus glycoprotein D that confer protective immunity.J.Virol.77, 9463–9473 (2003).

    Article  CAS  Google Scholar 

  • Bernstein D.I., Ashley R.L., Stanberry L.R., Myers M.G.: Detection of asymptomatic herpes simplex infections in animals immunized with subunit HSV glycoprotein vaccines.J.Clin.Microbiol.28, 11–15 (1990).

    PubMed  CAS  Google Scholar 

  • Bernstein D.I., Aoki F.Y., Tyring S.K., Stanberry L.R., St.Pierre C., Shafran S.D., Leroux-Roels G., Vanherck K., Bollaerts A., Dubin G.: Safety and immunogenicity of glycoprotein D-adjuvanted genital herpes vaccine.Clin.Infect.Dis.40, 1271–1281 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Blacklaw B.A., Nash A.A.: Immunological memory to herpes simplex virus type 1 glycoproteins B and D in mice.J.Gen.Virol.71, 863–871 (1990).

    Article  Google Scholar 

  • Bosch D.L., Geerligs H.J., Weijer W.J., Feijlbrief M., Welling G.W., Welling-Wester S.: Structural properties and reactivity of N-terminal synthetic peptides of herpes simplex virus type 1 glycoprotein D by using antipeptide antibodies and group VII monoclonal antibodies.J.Virol.61, 3607–3611 (1987).

    PubMed  CAS  Google Scholar 

  • Bourne N., Milligan G.N., Schleiss M.R., Bernstein D.I., Stanberry L.R.: DNA immunization confers protective immunity on mice challenged intravaginally with herpes simplex virus type 2.Vaccine14, 1230–1234 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Bourne N., Pyles R.B., Bernstein D., I., Stanberry L.R.: Modification of primary and recurrent genital herpes in guinea pigs by passive immunization.J.Gen.Virol.83, 2797–2801 (2002).

    PubMed  CAS  Google Scholar 

  • Bourne N., Bravo F.J., Francotts M., Bernstein D.I., Myers M., Slioui M., Stanberry L.: Herpes simplex virus type 2 glycoprotein D subunit vaccines and protection against genital HSV 1 and HSV 2 disease in guinea pigs.J.Infect.Dis.187, 542–548 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Broker M., Abel K.J., Kohler R., Hilfenhaus J., Amann E.:Escherichia coli-derived envelope protein gD but not gC antigens of herpes simplex virus protect mice against a lethal challenge with HSV-1 and HSV-2.Med.Microbiol.Immunol.179, 145–149 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Bryson Y.J., Winter H.S., Gard S.E., Fisher T.J., Stiehm E.R.: Deficiency of immune interferon production by leukocytes in normal newborns.Cell Immunol.55, 191–200 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Burke R.L., Goldbeck C., Ng P., Stanberry L., Ott G., Van Nest G.: The influence of adjuvant on the therapeutic efficacy of a recombinant genital herpes vaccine.J.Infect.Dis.170, 1110–1119 (1994).

    PubMed  CAS  Google Scholar 

  • Cantin E.M., Puga A., Notkins A.L.: Molecular biology of herpes simplex virus latency, pp. 172–178 in A.L. Notkins, M.B.A. Oldstone (Eds):Concepts in Viral Pathogenesis. Springer-Verlag, Berlin-Heidelberg 1984.

    Google Scholar 

  • Cantin E.M., Eberle R., Baldick J.L., Moss B., Willey D.E., Notkins A.L., Openshaw H.: Expression of herpes simplex virus glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus infection.Proc.Nat.Acad.Sci.USA84, 5908–5912 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Cappel R., Sprecher S., Cuyper de F., De Brakeleer J.: Clinical efficacy of a herpes simplex subunit vaccine.J.Med.Virol.16, 137–145 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Caselli E., Balboni P., Incorvaia C., Argnani R., Parmeggiani F., Cassai E., Manservigi R.: Local and systemic inoculation of DNA or protein gBs-based vaccines induce protective immunity against rabbit ocular infection.Vaccine19, 1225–1231 (2001a).

    Article  Google Scholar 

  • Caselli E., Grandi P., Argnani R., Balboni P.G., Selvatici R., Manservigi R.: Mice genetic immunization with plasmid DNA encoding a secreted form of HSV-1 gB induces a protective immune response against herpes simplex virus type 1 infection.Intervirology44, 1–7 (2001b).

    Article  PubMed  CAS  Google Scholar 

  • Chan W.L., Lukig M.L., Liew F.Y.: Helper T cells induced by and immunopurified herpes simplex virus type 1 115-kDa glycoprotein gB protect mice against HSV-1 infection.J.Exp.Med.162, 1304–1318 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Chapsal J.M., Pereira L.: Characterization of epitopes on native and denaturated forms of herpes simplex virus glycoprotein B.Virology164, 427–434 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Chen S.H., Kramer M.F., Schaffer P.A., Coen D.M.: A viral function represses accumulation of transcripts from productive cycle genes in mouse ganglia latently infected with herpes simplex virus.J.Virol.71, 5878–5884 (1997).

    PubMed  CAS  Google Scholar 

  • Chen S.H., Graber D.A., Schaffer P.A., Knipe D.M., Coen D.M.: Persistent elevated expression of cytokine transcripts in ganglia latently infected with herpes simplex virus in the absence of ganglionic replication or reactivation.Virology278, 207–216 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Chou J., Kern E.R., Whitley R.J., Roizman B.: Mapping of herpes simplex virus 1 neurovirulence to 34.5 gene nonessential for growth in culture.Science250, 1262–1266 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Cocchi F., Menom L., Dubreuil P., Lopez M., Campadelli-Fiume G.: Cell-to-cell spread of wild type herpes simplex virus type 1, but not of syncytial strains, is mediated by the immunoglobulin-like receptors that mediate virion entry, nectin 1 (PRRR1/HveC/HlgR) and nectin 2 (PRR2/HveB).J.Virol.74, 3909–3917 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Cohen G.H., Isola V.J., Kuhns J., Berman P.W., Eisenberg R.J.: Localization of discontinuous epitopes of herpes simplex virus glycoprotein D: use of a nondenaturing (“native” gel) system of polyacrylamide gel electrophoresis coupled with Western blotting.J.Virol.60, 157–166 (1987).

    Google Scholar 

  • Coles R.M., Mueller S.N., Heath S.N., Carbone F.R., Brooks A.G.: Progression of armed lymph node to spleen shortly after localized infection with herpes simplex virus 1.J.Immunol.168, 834–838 (2002).

    PubMed  CAS  Google Scholar 

  • Cose S.C., Kelly J.M, Carbone F.R.: Characterization of a diverse primary herpes simplex virus type 1 gB-specific cytotoxic T-cell response showing a preferential Vβ bias.J.Virol.69, 5849–5853 (1995).

    PubMed  CAS  Google Scholar 

  • Cunningham A.L., Noble J.R.: Role of keratinocytes in human recurrent herpetic lesions. Ability to present herpes simplex virus antigen and act as targets for T lymphocyte cytotoxicityin vitro.J.Clin.Invest.83, 490–496 (1989).

    Article  PubMed  CAS  Google Scholar 

  • DaCosta X.J., Bourne N., Stanberry L.R., Knipe D.M.: Construction and characterization of a replication defective herpes simplex virus 2 ICP8 mutant strain and its use in immunization studies in a guinea pig model of genital disease.Virology232, 1–12 (1997).

    Article  CAS  Google Scholar 

  • De Maria A., Tundo P., Romano A., Grima P.: Anti-HSV 1 herpes vaccination by Lupidon H: preliminary results.Adv.Exp.Med.Biol.371b, 1599–1600 (1995).

    PubMed  Google Scholar 

  • Deshpande S.P., Kumaraguru U., Rouse B.T.: Why do we lack an effective vaccine against herpes simplex virus infections?Microb.Infect.2, 973–978 (2000).

    Article  CAS  Google Scholar 

  • Dix R.D., Pereira L., Baringer J.R.: Use of uniform monoclonal antibody directed against herpes simplex virus glycoproteins to protect against acute virus-induced neurological disease.Infect.Immun.34, 192–199 (1981).

    PubMed  CAS  Google Scholar 

  • Duerst R.J., Morrison L.A.: Innate immunity to herpes simplex virus type 2.Viral Immunol.16, 475–489 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Dundarov S., Andonov P., Bakalov B., Nechev K., Tomov C.: Immunotherapy with inactivated polyvalent herpes vaccines.Develop.Biol.Standard.52, 351–358 (1982).

    CAS  Google Scholar 

  • Eisenberg R.J., Long D., Ponce L.M., Matthews J.T., Spear P.G., Gibson M.G., Lasky L.A., Berman P., Golub E., Cohen G.H.: Localization of epitopes of herpes simplex virus type 1 glycoprotein D.J.Virol.53, 634–644 (1985).

    PubMed  CAS  Google Scholar 

  • Efstathiou S., Minson A., Field H., Anderson J.R., Wildy P.: Detection of herpes simplex virus-specific DNA sequences in latently infected mice and humans.J.Virol.57, 446–455 (1986).

    PubMed  CAS  Google Scholar 

  • Erturk M., Jennings R., Hockley D., Potter C.W.: Antibody to herpes simplex type 1 antigen immune-stimulating complex preparations.J.Gen.Virol.70, 2149–2155 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Erturk M., Philipotts R.J., Welch M.J., Jennings R.: Efficacy of HSV-1 ISCOM vaccine in the guinea pig model of HSV-2 infection.Vaccine9, 728–733 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Fareell H.E., McLean C.S., Harley C., Efstathiou S., Inglis S., Minson A.C.: Vaccine potential of a herpes simplex virus type 1 with an essential glycoprotein deleted.J.Virol.68, 927–932 (1994).

    Google Scholar 

  • Fló J., Beatriz-Perez A., Tisminetzky S., Baralle F.: Superiority of intramuscular route and full length glycoprotein D vaccination against herpes simplex 2. Enhancement of protection by the codelivery of the GM-CSF gene.Vaccine18, 3242–3253 (2000).

    Article  PubMed  Google Scholar 

  • Fuller O.A., Spear P.G.: Anti-glycoprotein D antibodies that permit adsorption but block infection by herpes simplex virus 1 prevent virion-cell fusion at the cell surface.Proc.Nat.Acad.Sci.USA84, 5454–5458 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Forrester A., Farell H., Wilkinson G., Kaye J., Davis-Poynter N., Minson T.: Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted.J.Virol.66, 341–348 (1992).

    PubMed  CAS  Google Scholar 

  • Frye T.D., Chiou H.C., Hull B.E., Bigley N.J.: The efficacy of a DNA vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein D in decreasing ocular disease severity following corneal HSV-1 challenge.Arch.Virol.147, 1747–1759 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Gallichan W.S., Woolstencroft R.N., Guarasci T., McCluskie M.J., Davis H.L., Rosenthal K.L.: Intranasal immunization with CpG oligodeoxynucleotides as an adjuvant dramatically increases IgA and protection against herpes simplex virus-2 in the genital tract.J.Immunol166, 3451–3457 (2001).

    PubMed  CAS  Google Scholar 

  • Garnett G.P., Dubin G., Slaoui M., Darcis T.: The potential epidemiological impact of a genital herpes vaccine for women.Sex.Transm.Infect.80, 24–29 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Garber D.A., Schaffer P.A., Knipe D.M.: A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1.J.Virol.71, 5885–5893 (1997).

    PubMed  CAS  Google Scholar 

  • Gebhard R.J., Zhu J., Cao X., Minnick J., Araneo B.A.: DNA immunization utilizing a herpes simplex virus type 2 myogenic DNA vaccine protects mice from mortality and prevent genital herpes.Vaccine18, 1837–1846 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Ghiasi H., Kaiwar R., Nesburn A.B., Slanina S., Wechsler S.: Baculovirus-expressed glycoprotein E of herpes simplex virus type 1 protects mice against lethal intraperitoneal challenge and lethal ocular challenge.Virology188, 469–476 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Ghiasi H., Cai S., Perng G.C., Nesburn A.B., Wechsler S.L.: Both CD4 and CD8 T cells are involved in protection against HSV 1 induced corneal scarring.Brit.J.Ophthalmol.84, 408–412 (2000).

    Article  CAS  Google Scholar 

  • Hall M.J., Katrak K.: The quest for herpes simplex vaccine: background and recent developments.Vaccine4, 138–150 (1986).

    Article  PubMed  CAS  Google Scholar 

  • Hallford W.P., Gehardt B.M., Carr D.J.: Persistent cytokine expression in trigeminal ganglion latently infected with herpes simplex virus type 1.J.Immunol.157, 3542–3549 (1996).

    Google Scholar 

  • Harandi A.M., Svennerholm B., Holmgren J., Erickson K.: Protective vaccination against genital herpes simplex type 2 infection in mice is associated with a rapid induction of local IFN-γ dependent RANTES production following a vaginal viral challenge.Am.J.Reprod.Immunol.46, 420–424 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Herold B.C., Visalli R.J., Susmarski N., Brandt C.R., Spear P.G.: Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B.J.Gen.Virol.75, 1211–1222 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Higgins T.J., Herold K.M., Arnold R.L., McElhiney S.P., Shroff K.E., Pachuk C.J.: Plasmid DNA-expressed secreted and non-secreted forms of herpes simplex virus glycoprotein D2 induce different types of immune responses.J.Infect.Dis.182, 1311–1320 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Highlander S.L., Sutherland S.L., Gage P.J., Johnson D.C., Levine M., Glorioso J.C.: Neutralizing monoclonal antibodies specific for herpes simplex virus glycoprotein D inhibit penetration.J.Virol.61, 3356–3364 (1987).

    PubMed  CAS  Google Scholar 

  • Hilfenhaus J., Moser H.: Prospects for a subunit vaccine against herpes simplex virus infections.Behr.Inst.Mitt.69, 45–56 (1981).

    CAS  Google Scholar 

  • Hill A., Jugovich P., York I., Russ G., Bennink J., Yewdell J., Ploegh H., Johnson D.: Herpes simplex virus turns off the TAP to evade host immunity.Nature375, 411–415 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Hirsch M.S.B., Zisman B., Allison A.G.: Macrophages and age dependent resistance to herpes simplex virus in mice.J.Immunol.104, 1160–1165 (1970).

    PubMed  CAS  Google Scholar 

  • Hosken N.A.: Development of a therapeutic vaccine for HSV 2.Vaccine23, 2395–2398 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Howes E.L., Taylor W., Mitchison N.A., Simpson E.: MHC matching shows that at least two T cell subsets determine resistance to HSV.Nature277, 67–68 (1979).

    Article  Google Scholar 

  • Immuno Report: A Candidate Herpes Vaccine: HSV 1 Strain HSZP Subunit Vaccine, Adjuvanted. Immuno AG, Wien (Austria) 1995.

  • Inoue Y., Ohashi Y., Shimomura Y., Manabe R., Yamada M., Ueda S., Kato S.: Herpes simplex virus glycoprotein D. Protective immunity against murine herpetic keratitis.Invest.Ophthalmol.Visual Sci.31, 411–418 (1990).

    CAS  Google Scholar 

  • Inoue T., Inoue Y., Nakamura Y., Yoshida A., Inoue Y., Tano Y., Shimomura Y., Pujisawa Y., Aono A., Hayashi K.: The effect of immunization with herpes simplex virus glycoprotein D fused with interleukin 2 against murine herpetic keratitis.Japan.J.Ophthalmol.46, 370–376 (2001).

    Article  Google Scholar 

  • Isola V.J., Eisenberg R.J., Siebert G.R., Heilman C.J., Wilcox W.C., Cohen G.H.: Fine mapping of antigenic site II of herpes simplex virus glycoprotein D.J.Virol.63, 2325–2334 (1989).

    PubMed  CAS  Google Scholar 

  • Jacobson J.G., Ruffner K.L., Kosz-Vnenchak M., Hwang C.B.C., Wobbe K.K., Knipe D.M., Coen D.M.: Herpes simplex virus thymidine kinase and specific stages of latency in murine trigeminal ganglia.J.Virol.67, 6903–6908 (1993).

    PubMed  CAS  Google Scholar 

  • Jennings S.R., Rice P.L., Kloszewski E.D., Anderson R.W., Thompson D.L., Tevethia S.S.: Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells.J.Virol.56, 757–766 (1985).

    PubMed  CAS  Google Scholar 

  • Johnson D.C., Hill A.B.: Herpesvirus evasion of the immune system.Curr.Topics Microbiol.Immunol.323, 149–177 (1998).

    Google Scholar 

  • Johnson R.M., Laski D.W., Fitch F.W., Spear P.G.: Herpes simplex virus glycoprotein D is recognized as antigen by CD4+ and CD8+ T lymphocytes from infected mice.J.Immunol.145, 702–710 (1990).

    PubMed  CAS  Google Scholar 

  • Kavaklova L., Dundarov S., Andonov P., Bakalov B., Dundarova D., Brodvarova I.: Preparation and efficacy of antiherpes type 1 and 2 subunit vaccines.Acta Virol.30, 402–410 (1986).

    PubMed  CAS  Google Scholar 

  • Keadle T.L., Layock K.A., Morris K.A., Leib D.A., Morrison L.A., Pepose J.S., Stuart P.M.: Therapeutic vaccination withvhs minus herpes simplex virus reduces the severity of recurrent herpetic stromal keratitis in mice.J.Gen.Virol.83, 2361–2365 (2002).

    PubMed  CAS  Google Scholar 

  • Kern A.B., Schiff B.L.: Vaccine therapy in recurrent herpes simplex.Arch.Dermatol.89, 844–845 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Kino Y., Eto T., Nishiyama K., Ohtono N., Mori R.: Immunogenicity of purified glycoprotein B of herpes simplex virus.Arch.Virol.89, 69–80 (1986).

    Article  PubMed  CAS  Google Scholar 

  • Klein R.J.: Initiation and maintenance of latent herpes simplex virus infections: the paradox of perpetual immobility and continuous movement.Rev.Infect.Dis.7, 21–30 (1985).

    PubMed  CAS  Google Scholar 

  • Klein R.J., Buimovici-Klein E., Moser H., Moucha R., Hilfenhaus J.: Efficacy of a virion envelope herpes simplex virus vaccine against experimental skin infections in hairless mice.Arch.Virol.68, 73–81 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Koelle D.M., Chen H.B., Gavin M.A., Wald A., Kwok W.W., Corey L.: CD8 CTL from genital herpes lesions: recognition of viral tegument and immediate early proteins and lysis of infected cutaneous cells.J.Immunol.166, 4049–4058 (2001).

    PubMed  CAS  Google Scholar 

  • Kohl S., Harmon M.W.: Human neonatal leukocyte interferon production and natural killer cytotoxicity in response to herpes simplex virus infected cells.J.Interferon Res.3, 461–463 (1983).

    PubMed  CAS  Google Scholar 

  • Kramer M.F., Coen D.M.: Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia latently infected with herpes simplex virus.J.Virol.69, 1389–1397 (1995).

    PubMed  CAS  Google Scholar 

  • Kuklin N., Daheshia M., Karem K., Manickan E., Rouse B.T.: Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization.J.Virol.71, 3138–3145 (1997).

    PubMed  CAS  Google Scholar 

  • Kumel G., Kaerner H.C., Schroder C.H., Glorioso J.C.: Passive immune protection by herpes simplex virus-specific monoclonal antibodies and monoclonal antibody resistant mutants altered in pathogenicity.J.Virol.56, 930–937 (1985).

    PubMed  CAS  Google Scholar 

  • Kutinova L., Benda R., Kalos Z., Dbalý V., Votruba T., Kvíčalová E., Petrovská P., Doutlík S., Kamínková J., Domorazková E.: Placebo controlled study with subunit herpes simplex virus vaccine in subjects suffering from frequent herpetic recurrences.Vaccine6, 223–228 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Lachmann R.H., Sadarangani M., Atkinson H.R., Efstathiou S.: An analysis of herpes simplex virus gene expression during latency establishment and reactivation.J.Gen.Virol.80, 1271–1282 (1999).

    PubMed  CAS  Google Scholar 

  • Larsen H.S., Russel R.G., Rouse B.T.: Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic lymphocytes.Infect.Immun.41, 197–204 (1983).

    PubMed  CAS  Google Scholar 

  • Lasky L.A., Dowbenko D., Simonsen C.C., Berman P.W.: Protection of mice from lethal herpes simplex virus infection by vaccination with a secreted form of cloned glycoprotein D.Biotechnology2, 527–532 (1984).

    Article  CAS  Google Scholar 

  • Lavelle E.C., Grant G., Pusztai A., Pfuller U., Leavy O., McNeela E., Mills H.G., Hagan D.T.: Mistloe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2.Immunology107, 268–274 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Lee H.H., Cha S.C., Jang D.J., Lee J.K., Cho D.W., Kim Y.S., Uh H.S., Kim S.Y.: Immunization with combined HSV-2 glycoproteins B2:D2 gene DNAs: protection against lethal intravaginal challenges in mice.Virus Genes25, 179–188 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Lee S., Gierynska M., Eo S.K., Kuklin N., Rouse B.T.: Influence of DNA encoding cytokines on systemic and mucosal immunity following genetic vaccination against herpes simplex virus.Microbes Infect.5, 571–578 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Liu T., Tang Q., Hendricks R.L.: Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection.J.Virol.70, 264–271 (1996).

    PubMed  CAS  Google Scholar 

  • Liu T., Khanna K.M., Chen X.P., Fink J.D., Hendricks R.L.: CD8+ T cells can block herpes simplex virus type 1 reactivation from latency in sensory neurons.J.Exp.Med.191, 1459–1466 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Long D., Madara T., Ponce de Leon M., Cohen G.H., Montgomery P.C., Eisenberg R.J.: Glycoprotein D protects mice against lethal challenge with herpes simplex virus types 1 and 2.Infect.Immun.37, 761–764 (1984).

    Google Scholar 

  • Manservigi R., Grossi M.P., Gualandri R., Balboni P.G., Marchini P.G., Rotola A., Rimessi P., Diluca D., Barbanti-Brodano G.: Protection from herpes simplex virus type 1 lethal and latent infections by secreted recombinant glycoprotein B constitutively expressed in human cells with a BK virus episomal vector.J.Virol.64, 431–436 (1990).

    PubMed  CAS  Google Scholar 

  • Manservigi R., Boreo A., Argnani R., Caselli E., Zucchini S., Miriagu V., Mavromara P., Cilli M., Grossi M.P., Balboni V., Cassai E.: Immunotherapeutic activity of a recombinant combined gB-gD-gE vaccine against recurrent HSV 2 infections in a guinea pig model.Vaccine23, 865–872 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Marlin S.D., Highlander S.L., Holland T.C., Levine M., Glorioso J.C.: Antigenic variation (mar mutations) in herpes simplex virus glycoprotein B can induce temperature-dependent alterations in gB processing and virus production.J.Virol.59, 142–153 (1986).

    PubMed  CAS  Google Scholar 

  • Martin S., Rouse B.T.: The mechanimsm of antiviral immunity induced by vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D clearance of local infection.J.Immunol.138, 3431–3437 (1987).

    PubMed  CAS  Google Scholar 

  • Martin S., Courtney R.J., Fowler G., Rouse B.T.: Herpes simplex virus type 4 specific cytotoxic T lymphocytes recognize virus nonstructural proteins.J.Virol.62, 1359–1370 (1989).

    Google Scholar 

  • McClements W.L., Armstrong M.E., Keys R.D., Liu M.A.: The prophylactic effect of immunization with DNA encoding herpes simplex virus glycoproteins on HSV-induced disease in guinea pigs.Vaccine15, 857–860 (1997).

    Article  PubMed  CAS  Google Scholar 

  • McDermott M.R., Goldsmith C.H., Rosenthal K.S., Braus L.J.: T lymphocytes in the genital lymph nodes protect mice from intravaginal infection with herpes simplex virus type 2.J.Infect.Dis.159, 460–466 (1989).

    PubMed  CAS  Google Scholar 

  • McLaughlin-Taylor E., Willey D.E., Cantin E.M., Eberle R., Moss B., Openshaw H.: A recombinant vaccinia virus expressing herpes simplex virus type 1 glycoprotein B induces cytotoxic T lymphocytes in mice.J.Gen.Virol.69, 1731–1734 (1988).

    Article  PubMed  CAS  Google Scholar 

  • McLean C.S., Ertirk M., Jennings R.: Protective vaccination against primary and recurrent primary disease caused by herpes simplex virus type 2 using a genetically disabled HSV 1.J.Infect.Dis.170, 1100–1109 (1994).

    PubMed  CAS  Google Scholar 

  • Meignier B., Jourdier T.M., Norrild B., Roizman B.: Immunization of experimental animals with reconstituted glycoprotein mixtures of herpes simplex virus 1 and 2: protection against challenge with virulent virus.J.Infect.Dis.155, 921–930 (1987).

    PubMed  CAS  Google Scholar 

  • Mertz G.J., Ashley R., Burke R.I., Benedetti J., Critchlow C., Jones C.C., Corey L.: Double blind placebo controlled trial of a herpes simplex virus type 2 glycoprotein vaccine in persons at high risk for genital herpes infection.J.Infect.Dis.161, 653–660 (1990).

    PubMed  CAS  Google Scholar 

  • Mester J.C., Rouse B.T.: The mouse model and understanding immunity to herpes simplex virus.Rev.Infect.Dis.13, 935–945 (1991).

    Google Scholar 

  • Mester J.C., Glorioso J.C., Rouse B.T.: Protection against the zosteriform spread of herpes simplex virus glycoproteins.J.Infect.Dis.163, 263–269 (1990).

    Google Scholar 

  • Metcalf J.F., Whitley R.F.: Protective immunity against herpetic ocular disease in an outbred mouse model.Curr.Eye Res.6, 167–171 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Milligan G.N., Bernstein D.I.: Analysis of herpes simplex virus-specific T cells in the murine female genital tract following genital infection with herpes simplex virus type 2.Virology212, 481–489 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Mishkin E.M., Fahey J.R., Kino Y., Klein R.J., Abramovitz A.S., Mento S.J.: Native herpes simplex virus glycoprotein D vaccine: immunogenicity and protection in animal model.Vaccine9, 147–153 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Mohamedi S.A., Heath A.W., Jennings H.R.: A comparison of oral and parenteral routes for therapeutic vaccination with HSV-2 ISCOM in mice: cytokine profiles, antibody responses and protection.Antiviral Res.49, 83–99 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Morrison L.A., Knipe D.M.: Mechanisms of immunization with a replication-defective mutant of herpes simplex virus 1.Virology220, 402–413 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Mossman K.L., Safran H.A., Smiley J.R.: Herpes simplex virus ICP0 mutants are hypersensitive in interferon.J.Virol.74, 2052–2056 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Mueller S.N., Jones C.M., Smith C.M., Heath W.R., Carbone F.R.: Rapid cytotoxic lymphocyte activation in the draining lymph nodes after cutaneous herpes simplex virus infection as a result of early antigen presentation and not the presence of virus.J.Exp.Med.195, 651–656 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Mueller S.N., Jones C.M., Chen W., Kawaika Y., Castrucci M.R., Heath W.R., Carbone F.R.: The early expression of glycoprotein B from herpes simplex virus can be detected by antigen-specific CD8/T cells.J.Virol.77, 2445–2451 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Muggeridge M.I., Wu T.T., Johnson D.C., Glorioso J.C., Eisenberg R., Cohen G.H.: Antigenic and functional analysis of a neutralization site of HSV-1 glycoprotein D.Virology174, 375–387 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Myers M.G., Bernstein D., Harrison C.J., Stanberry L.R.: Herpes simplex virus glycoprotein treatment of recurrent genital herpes reduces cervicovaginal virus shedding in guinea pigs.Antiviral Res.10, 83–88 (1988).

    Article  PubMed  CAS  Google Scholar 

  • Nagafuchi S., Hayashida I., Higa K., Wada T., Mori T.: Role of lyt 1 positive immune T cells in recovery from herpes simplex virus infection in mice.Microbiol.Immunol.26, 359–362 (1982).

    PubMed  CAS  Google Scholar 

  • Nash A.: Comentary. T cells and the regulation of herpes simplex virus latency and reactivation.J.Exp.Med.191, 1455–1457 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Nash A.A., Phelan J., Wildy P.: Cell mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed type hypersensitivity response and the antiviral T cell response.J.Immunol.126, 1260–1262 (1981).

    PubMed  CAS  Google Scholar 

  • Nash A.A., Gell P.G.H.: Membrane phenotype of murine effector and suppressor T cells involved in delayed hypersensitivity and protective immunity to herpes simplex virus.Cell Immunol.75, 348–355 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Nash A.A., Jayashuria A., Phelan J., Cobbold S.P., Waldmann H., Prospero T.: Different roles for L3T4+ and Lyt-2+ cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system.J.Gen.Virol.68, 825–833 (1987).

    Article  PubMed  Google Scholar 

  • Nass P.H., Elkins K.L., Weir J.P.: Protective immunity against herpes simplex virus generated by DNA vaccination compared to natural infection.Vaccine19, 1538–1546 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Nguyen L.H., Knipe D.M., Finberg R.W.: Replication defective mutants of herpes simplex virus induce cellular immunity and protect against lethal HSV infection.J.Virol.66, 7067–7072 (1992).

    PubMed  CAS  Google Scholar 

  • Novak E.J., Maseqicz S.A., Liu A.W., Lernmark A., Kwok W.W., Nepom G.T.: Activated human epitope specific T cells identified by class II tetramers reside within a CD4 high proliferating subset.Internat.Immunol.13, 799–800 (2000).

    Article  Google Scholar 

  • Oakes J.E., Lausch R.N.: Monoclonal antibodies suppress replication of herpes simplex virus type 1 in trigeminal ganglia.J.Virol.51, 656–661 (1984).

    PubMed  CAS  Google Scholar 

  • Osorio Y., Cohen J., Ghiasi H.: Improved protection from primary ocular HSV 1 infection and establishment of latency using multigenic DNA vaccines.Invest.Ophthalm.Visual Sci.45, 506–514 (2004).

    Article  Google Scholar 

  • Paine T.F.: Latent herpes simplex infection in man.Bact.Rev.28, 472–479 (1964).

    PubMed  Google Scholar 

  • Parr M.B., Kepple L., McDermott M.R., Drew M.D., Bozzola J.J., Parr E.L.: A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2.Lab.Invest.70, 369–380 (1994).

    PubMed  CAS  Google Scholar 

  • Pereira L., Ali M., Kousoulas K., Huo B., Banks T.: Domain structure of herpes simplex virus 1 glycoprotein B: neutralizing epitopes map in regions of continuous and discontinues residues.Virology172, 11–24 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Posavad C.M., Huang M.L., Barey S., Koelle D.M., Corey L.: Long term persistence of herpes simplex virus-specific CD8 cytotoxic lymphocytes with frequently recurring genital herpes.J.Immunol.165, 1146–1152 (2000).

    PubMed  CAS  Google Scholar 

  • Preston C.M.: Repression of viral transcription during herpes simplex virus latency.J.Gen.Virol.81, 1–9 (2000).

    PubMed  CAS  Google Scholar 

  • Rajčáni J.: DNA regions and genes determining the virulence of herpes simplex virus.Acta Virol.36, 208–222 (1992).

    PubMed  Google Scholar 

  • Rajčáni J., Ďurmanová V.: Early expression of herpes simplex virus proteins and reactivation of latent infection.Folia Microbiol.45, 7–28 (2000).

    Article  Google Scholar 

  • Rajčáni J., Szántó J.: Persistent and latent infections with herpes simplex virus. (In Slovak)Biol.Listy41, 161–171 (1976).

    Google Scholar 

  • Rajčáni J., Vojvodová A.: The role of herpes simplex virus glycoproteins in the virus replication cycle.Acta Virol.42, 103–118 (1998).

    PubMed  Google Scholar 

  • Rajčáni J., Čiampor F., Sabó A., Libíková H., Rosenbergová M.: Activation of latent herpesvirus hominis in explants of rabbit trigeminal ganglia: the influence of immune serum.Arch.Virol.53, 55–69 (1977).

    Article  PubMed  Google Scholar 

  • Rajčáni J., Kutinová L., Vonka V.: Restriction of latent herpes virus infection in rabbits immunized with a subviral herpes simplex virus vaccine.Acta Virol.24, 183–193 (1980).

    PubMed  Google Scholar 

  • Rajčáni J., Matis J., Kúdelová M., Leško J., Reichel M., Fuchsberger N., Leššo J.: A simple novel procedure for preparation of herpes virus subunit vaccine.Acta Virol.32, 317–328 (1988).

    PubMed  Google Scholar 

  • Rajčáni J., Herget U., Košťál M., Kaerner H.C.: Latency competence of herpes simplex virus strains ANG, ANGpath and their gC and gE mutants.Acta Virol.34, 477–486 (1990).

    PubMed  Google Scholar 

  • Rajčáni J., Sabó A., Mucha V., Compel P., Košťál M.: Herpes simplex type 1 subunit vaccine not only protects against lethal virus challenge, but also restricts latency and reactivation.Acta Virol.39, 37–49 (1995).

    PubMed  Google Scholar 

  • Rajčáni J., Moško T., Režuchová I.: Current developments in viral DNA vaccines: shall they solve the unsolved?Rev.Med.Virol.15, 1–23 (2005).

    Article  CAS  Google Scholar 

  • Rector J.T., Lausch R.N., Oakes J.E.: Use of monoclonal antibodies for analysis of antibody dependent immunity to ocular herpes simplex virus type 1 infection.Infect.Immun.38, 168–174 (1982).

    PubMed  CAS  Google Scholar 

  • Režuchová I., Kúdelová M., Ďurmanová V., Vojvodová A., Košovský J., Rajčáni J.: Transcription at carly stages of herpes simplex virus infection and during reactivation.Intervirology46, 25–34 (2003).

    Article  PubMed  Google Scholar 

  • Roberts P.L., Duncan B.E., Raybold G.J., Watson D.H.: Purification of herpes simplex virus glycoproteins B and C using monoclonal antibodies and their ability to protect mice against lethal challenge.J.Gen.Virol.66, 1073–1085 (1985).

    Article  PubMed  CAS  Google Scholar 

  • Rock D.L., Nesburn A.B., Ghiasi H., Ong J., Lewis T.L., Lockensgrad J.R., Wechsler S.L.: Detection of latency-related viral RNAs in trigeminal ganglia of rabbits latently infected with herpes simplex virus type 1.J.Virol.61, 3280–3286 (1987).

    Google Scholar 

  • Rogers J.V., Bigley N.J., Chiou H.C., Hull B.E.: Targeted delivery of DNA encoding herpes simplex virus type-1 glycoprotein D enhances the cellular response to primary viral challenge.Arch.Dermatol.Res.292, 542–549 (2000a).

    Article  PubMed  CAS  Google Scholar 

  • Rogers J.V., Hull B.E., Fink P.S., Chiou H.C., Bigley N.J.: Murine response to DNA encoding herpes simplex virus type-1 glycoprotein D targeted to the liver.Vaccine18, 1522–1530 (2000b).

    Article  PubMed  CAS  Google Scholar 

  • Roizman B., Knipe D.M.: Herpes simplex viruses and their replication, pp. 2399–2460 in D.M. Knipe, P.M. Howley (Eds):Fields Virology, 4th ed. Lippincott-Williams & Wilkins, Philadelphia-Baltimore-New York-London-Buenos Airees-Hong Kong-Sydney-Tokyo 2001.

    Google Scholar 

  • Rooney J.F., Eohlenberg C.H., Cremer K.J., Moss B., Notkins A.L.: Immunization with a vaccinia virus recombinant expressing herpes simplex virus glycoprotein D: long-term protection and effect of revaccination.J.Virol.62, 1530–1534 (1988).

    PubMed  CAS  Google Scholar 

  • Rouse B., Gierynska M.: Immunity to herpes simplex virus: a hypothesis.Herpes8 (Suppl. 1), 2–5 (2001).

    Google Scholar 

  • Rouse B.T., Nair S., Rouse R.J., Yu Z., Kuklin N., Karem K., Manickan M.: DNA vaccines and immunity to herpes simplex virus.Curr.Topics Microbiol.Immunol.226, 69–78 (1998).

    CAS  Google Scholar 

  • Salio M., Cella M., Suter M., Lanzavieccha A.: Inhibition of dendritic cell maturation by herpes simplex virus.Eur.J.Immunol.29, 3245–3253 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Sanches-Pescador L., Burke R.L., Ou G., Van Nest G.: The effect of adjuvants on the efficacy of a recombinant herpes simplex virus glycoprotein vaccine.J.Immunol.141, 1720–1727 (1988).

    Google Scholar 

  • Sander G., Sander U.: Untersuchung einer Subunit Vakzine an der rezidivierenden kutanen Herpes simplex Virus Typ I Infektion der Maus.Diplomarbeit. Institut für Medizinische Mikrobiologie, Medizinische Akademie Erfurt, Erfurt 1991.

    Google Scholar 

  • Schneweis K.E., Gruber J., Hilfenhaus J., Moslein A., Kayser M., Wolff M.H.: The influence of different modes of immunization on the experimental genital herpes simplex virus infection in mice.Med.Microbiol.Immunol.169, 269–279 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Sciammas R., Johnson R.M., Sperling A.I., Brady W., Linsley P.S., Spear P.G., Fitch F.W., Bluestone J.A.: Unique antigen recognition by herpes specific TCR-γ/δ cell.J.Immunol.152, 5392–5397 (1994).

    PubMed  CAS  Google Scholar 

  • Scriba M.: Persistence of herpes simplex virus (HSV) infection in ganglia and peripheral tissues of guinea pigs.Med.Microbiol.Immunol.169, 91–96 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Scriba M.: Animal studies on the efficacy of vaccination against recurrent herpes.Med.Microbiol.Immunol.171, 33–42 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Shimeld C.J., Whiteland J.J., Williams N.A., Easty D.I., Hill T.J.: Cytokine production in the nervous system of mice during acute and latent infection with herpes simplex virus type 1.J.Gen.Virol.78, 3317–3325 (1997).

    PubMed  CAS  Google Scholar 

  • Simmons A., Tscharke D.: Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications and the fate of virally infected neurons.J.Exp.Med.175, 1337–1344 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Simons A.A., Nash A.A.: Role of antibody in primary and recurrent herpes simplex virus infection.J.Virol.53, 944–948 (1985).

    Google Scholar 

  • Sin J.I., Kim J.J., Arnold R.L., McCallus D., Pachuk C., McElhiney S.P., Wolf M.W., Pompa de Bruin S.J., Higgins T.J., Ciccarelli R.B., Weiner D.B.: IL-12 gene as a DNA vaccine adjuvant in a herpes mouse model: IL-12 enhances Th1-type CD4+ T cell-mediated protective immunity against herpes simplex virus-2 challenge.J.Immunol.162, 2912–2921 (1999).

    PubMed  CAS  Google Scholar 

  • Sin J., Kim J.J., Pachuk C., Satishchadran C., Weiner D.B.: DNA vaccines encoding interleukin-8 and RANTES enhance antigen-specific Th1-type CD4(+) T-cell-mediated protective immunity against herpes simplex virus type 2in vivo.J.Virol.74 11173–11180 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Singh M., Carlson J.R., Briones M.: A comparison of biodegradable microparticles and MF59 as systematic adjuvants for recombinant gD from HSV 2.Vaccine16, 1822–1827 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Skinner G.R., Buchan A., Hartley C.E., Turner S.P., Williams D.R.: The preparation efficacy and safety of antigenoid vaccine NFU1(S-L+) MRC toward prevention of herpes simplex virus infections in human subjects.Med.Microbiol.Immunol.169, 39–45 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Skinner G.R., Woodman C., Hartley C., Buchan A., Fuller A., Wiblin C., Wilkins G., Melling J.: Early experience with antigenoid vaccine AcNFU1 (S−) MRC towards prevention and modification of herpes genitalis.Develop.Biol.Standard.52, 333–344, (1982).

    CAS  Google Scholar 

  • Šlichtová V., Kutinová L., Vonka V.: Immunogenicity of a subviral herpes simplex type 1 preparation: reduction of recurrent disease in mice.Arch.Virol.71, 75–78 (1982).

    Article  PubMed  Google Scholar 

  • Smith C.M., Belz G.T., Wilson N.S., Villadangos J.A., Shortman K., Carbone F.R., Heath W.R.: Cutting edge: conventional CD8α+ dendritic cells are preferentially involved in CTL priming after footpad infection with herpes simplex virus I.J.Immunol.1, 4437–4440, (2003).

    Google Scholar 

  • Spear P.G., Eisenberg R.J., Cohen G.H.: Three classes of cell surface receptors for alphaherpesvirus entry.Virology275, 1–5 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Speck P., Simmons A.: Precipitous clearance of herpes simplex virus antigens from the peripheral nervous systems of experimentally infected C57BL/6 mice.J.Gen.Virol.79, 561–564 (1998).

    PubMed  CAS  Google Scholar 

  • Spivack J.G., Fraser N.W.: Expression of herpes simplex virus type 1 latency-associated transcripts in the trigeminal ganglia of mice during acute infection and reactivation of latent infection.J.Virol.62, 1479–1485 (1988).

    PubMed  CAS  Google Scholar 

  • Stanberry L.R.: Herpes simplex virus vaccines.Semin.Pediatr.Infect.Dis.2, 178–185 (1991a).

    Google Scholar 

  • Stanberry L.R.: Subunit viral vaccines: therapeutic and prophylactic uses, pp. 309–341 in I. Aurelian (Ed.):Herpesviruses, Immune System and AIDS. Kluwer Academic Publishers, Boston 1991b.

    Google Scholar 

  • Stanberry L.R.: The pathogenesis of herpes simplex virus infections, pp. 31–48 in L.R. Stanberry (Ed.):Genital and Neonatal Herpes. John Wiley & Sons, Chichester 1996.

    Google Scholar 

  • Stanberry L.R.: Genital and perinatal herpes simplex virus infections: prophylactic vaccines, pp. 187–216 in L.R. Stanberry, D.I. Bernstein (Eds):Sexually Transmitted Diseases, Vaccines, Prevention and Control. Academic Press, London 2000.

    Google Scholar 

  • Stanberry L.R.: Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines.Herpes11 (Suppl. 3), 161A-169A (2004).

    PubMed  Google Scholar 

  • Stanberry L.R., Bernstein D.I.: Pathogens and vaccines, pp. 185–457 in L.R. Stanberry, D.I. Bernstein (Eds):Sexually Transmitted Diseases, Vaccines, Prevention and Control. Academic Press, London 2000.

    Google Scholar 

  • Stanberry L.R., Bernstein D.I., Burke R.L., Pachl C., Myers M.G.: Recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes.J.Infect.Dis.155, 914–920 (1987).

    PubMed  CAS  Google Scholar 

  • Stanberry L.R., Myers M.G., Stephanopoulos D.I., Burke R.L.: Preinfection prophylaxis with herpes simplex virus glycoprotein immunogens: factors influencing efficacy.J.Med.Virol.70, 3177–3185 (1989).

    CAS  Google Scholar 

  • Stanberry L.R., Spruance S.L., Cunningham A.L., Bernstein D.I., Mindel A., Sacks S., Tyring S., Aoki F.Y., Slaoui M., Denis M., Vanpeliere P., Dubin G.: Glycoprotein D-adjuvant vaccine to prevent genital herpes.New Engl.J.Med.21, 1652–1661 (2002).

    Article  Google Scholar 

  • Stevens J.G.: Latent herpes simplex virus and the nervous system.Curr.Topics Microbiol.Immunol.70, 31–50 (1975).

    CAS  Google Scholar 

  • Strasser J.E., Arnold R.L., Pachuk C., Higgins T.J., Bernstein D.I.: Herpes simplex virus DNA vaccine efficacy: effect of glycoprotein D plasmid constructs.J.Infect.Dis.182, 1304–1310 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Straus S.E., Corey L., Burke R.L., Savarese B., Barnum G., Krause P.R., Kost R.G., Meier J.L., Sekulovich R., Adair S.F.: Placebo controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes.Lancet343, 1460–1463 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Straus S.E., Wald A., Kost R.G., McKenzie R., Langenberg A.G., Hohman P., Lekstrom J., Cox E., Nakamura M., Sekulovich R., Izu A., Dekker C., Corey L.: Immunotherapy of recurrent genital herpes with recombinant herpes simplex virus type 2 glycoprotein D and B: results of a placebo controlled vaccine trial.J.Infect.Dis.176, 1129–1234 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Succato G., Wald A., Wakabayashi E., Vieira J., Corey L.: Evidence of latency and reactivation of both herpes simplex virus HSV-1 and HSV-2 in the genital infection.J.Infect.Dis.177, 1069–1072 (1998).

    Google Scholar 

  • Sullender W.M., Miller J.L., Yasukawa L.L., Bradley J.S., Black S.B., Yeager A.S., Arvin A.M.: Humoral and cell mediated immunity in neonates with herpes simplex virus infection.J.Infect.Dis.155, 28–37 (1987).

    PubMed  CAS  Google Scholar 

  • Taylor J.L., Little S.D., O’Brien W.J.O.: The comparative anti-herpes simplex virus effect of human interferons.J.Inter.Cytok.Res.18, 159–165 (1998).

    CAS  Google Scholar 

  • Tenser R.B.: Role of herpes simplex virus thymidine kinases expression in viral pathogenesis and latency.Intervirology32, 76–92 (1991).

    PubMed  CAS  Google Scholar 

  • Theil D., Derfuss T., Paripovic I., Herberger S., Meinl E., Schueler O., Strupp M., Arbusov V., Brandl T.: Latent herpesvirus infection in human trigeminal ganglia causes chronic immune response.Am.J.Pathol.163, 2179–2184 (2003).

    PubMed  CAS  Google Scholar 

  • Thomson T.A., Hilfenhaus J., Moser H., Morahan P.S.: Comparison of effects of adjuvants on efficacy of herpes simplex virus vaccine against labial infection of Balb/c mice.Infect.Immun.41, 556–562 (1983).

    PubMed  CAS  Google Scholar 

  • Thornton B., Griffiths J.B., Walkland A.: Herpes simplex virus vaccine using cell membrane associated antigen in an animal model.Develop.Biol.Standard.50, 201–206 (1982).

    Google Scholar 

  • Tullo A.B., Shimeld C., Blyth C., Hill T.J., Easty D.L.: Spread of virus and distribution of latent infection following ocular herpes simplex in the non-immune and immune mouse.J.Gen.Virol.63, 95–101 (1982).

    Article  PubMed  Google Scholar 

  • Vandepapeliere P.: Therapeutic vaccines for control of herpes simplex virus chronic infections, pp. 217–238 in L.R. Stanberry, D.I. Bernstein (Eds):Sexually Transmitted Diseases. Vaccines, Prevention and Control. Academic Press, London 2000.

    Google Scholar 

  • Wachsman M., Luo J.H., Aurelian L., Perkus M.E., Paoletti E.: Antigen presenting capacity of epidermal cells infected with vaccinia virus recombinants containing the herpes simplex virus glycoprotein D and protective immunity.J.Gen.Virol.70, 2513–2520 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Wachsman M., Kulka M., Smith C.C., Aurelian L.: A growth and latency compromised herpes simplex type 2 mutant (ICP10/delPK) has prophylactic and therapeutic protective activity in guinea pigs.Vaccine19, 1879–1890 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Wallace M.E., Keating R., Heath W.R., Carbone F.R.: The cytotoxic T-cell response to herpes simplex virus type 1 infection of C57BL/6 mice is almost entirely directed against a single immunodominant determinant.J.Virol.73, 7619–7626 (1999).

    PubMed  CAS  Google Scholar 

  • Wildy P., Gell P.G.H.: The host response to herpes simplex virus.Brit.Med.Bull.41, 86–91 (1985).

    PubMed  CAS  Google Scholar 

  • Willey D.U., Cantin E.M., Hill L.R., Moss B., Notkins A.L., Openshaw H.: Herpes simplex type 1 vaccinia virus recombinant expressing glycoprotein B: protection from acute and latent infection.J.Infect.Dis.158, 1382–1386 (1989).

    Google Scholar 

  • Weitgasser H.: Kontrollierte klinische Studie mit den Herpes Antigenen Lupidon H and Lupidon G.G.Z.Hautkrank.52, 625–628 (1977).

    CAS  Google Scholar 

  • Whitbeck J.C.H., Peng C.H., Lou H., Xu R., Willis S.H., Ponce de Leon M., Peng T., Nicola A.V., Mongomery R.I., Warner M.S., Soulika A.M., Spruce L.A., Moore W.T., Lambris J.D., Spear P.G., Cohen G.H., Eisenberg R.J.: Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, a member of tumor necrosis factor receptor subfamily and mediator of HSV entry.J.Virol.71, 6083–6093 (1997).

    PubMed  CAS  Google Scholar 

  • Whitley R.J., Kern E.R., Chatterjee S., Chou J., Roizman B.: Replication establishment of latency, and induced reactivation of herpes simplex virus γ34.5 deletion mutants in rodent models.J.Clin.Invest.91, 2837–2843 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Whitley R.J.: Herpes simplex vaccines, pp. 727–747 in M.M. Levine, G.C. Woodrow, J.B. Capper, G.S. Cohen (Eds):New Generation of Vaccines, 2nd ed. Marcel Dekker, New York 1997.

    Google Scholar 

  • Whitley R.J.: Herpes simplex viruses, pp. 2461–2510 in D.M. Knipe, P.M. Howley (Eds):Fields Virology, 4th ed. Lippincott-Williams & Wilkins, Philadelphia-Baltimore-New York-London-Buenos Airees-Hong Kong-Sydney-Tokyo 2001.

    Google Scholar 

  • York I.A., Roop C., Andrew D.W., Riddel S.R., Graham F.L., Johnson D.C.: A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes.Cell77, 525–535 (1994).

    Article  PubMed  CAS  Google Scholar 

  • York L.J., Giorgio D., Mishkin E.M.: Immunomodulatory effects of HSV 2 glycoprotein D in HSV-1 infected mice: implications for immunotherapy of recurrent infection.Vaccine13, 1706–1712 (1995).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Virology, Slovak Academy of Sciences, 845 05, Bratislava, Slovakia

    J. Rajčáni & V. Ďurmanová

Authors
  1. J. Rajčáni
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. V. Ďurmanová
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to J. Rajčáni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rajčáni, J., Ďurmanová, V. Developments in herpes simplex virus vaccines: Old problems and new challenges. Folia Microbiol 51, 67–85 (2006). https://doi.org/10.1007/BF02932160

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02932160

Keywords