Immunisation against HSV-1 keratitis with a synthetic gD peptide

Abstract

The authors tested the protective efficacy of, and the immune response to, immunisation with a synthetic peptide of glycoprotein D (gD) of HSV-1 in a murine model of herpes stromal keratitis (HSK). HSV-1 susceptible A/J mice were immunised subcutaneously with a peptide corresponding to the N-terminal epitope gD(5-23) prior to corneal HSV-1 challenge. Divergent immunisation protocols were compared for their protective potency, their ability to prevent the establishment of latency in the trigeminal ganglion, and their effect on the immune system. Low dosages (31 µg) of gD(5-23) protected against encephalitis and HSK. Protective efficacy was higher when gD(5-23) was coupled to the carrier protein keyhole limpet haemo-cyanin (KLH) and was emulsified with adjuvant. Latent infection was found in all control mice but in only 50-75% of immunised mice. The most potent protection was correlated with anti-HSV-1 neutralising antibodies of IgG1 and IgG2a isotypes, but free gD(5-23) protected in the absence of anti-HSV-1 antibodies. Our results suggest that immunisation with gD(5-23) stimulates both humoral and cellular immune mechanisms which protect against HSV-1 keratitis.

References

  1. 1

    Dawson C, Togni G . Herpes simplex eye infections. Surv Ophthalmol 1976;21:11–29.

  2. 2

    Richards DM, Carmine AA, Brodgen RN, Heel RC, Speight TM, Avery GS . Acyclovir: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1983;26:378–438.

  3. 3

    Chapin CH, Wong SC, Reapsome J . The value of tissue culture vaccine in the prophylaxis of recurrent attacks of herpetic keratitis. Am J Ophthalmol 1962;54:255–65.

  4. 4

    Price RW, Katz BJ, Notkins AL . Latent infection of the peripheral ANS with herpes simplex virus. Nature 1975;257:686–8.

  5. 5

    Meignier B . Vaccination against herpes simplex virus infections. In: Roizman B, Lopez C, editors. The herpes viruses. New York: Plenum Publishing, 1984:265–96.

  6. 6

    Rawls WE . Herpes simplex viruses and their role in human cancer. In: Roizman B, Lopez C, editors. The herpes viruses. New York: Plenum Publishing, 1984:241–55.

  7. 7

    Cremer KJ, Mackett M, Wohlenberg C, Notkins AL, Moss B . Vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D prevents latent herpes in mice. Science 1985;228:737–40.

  8. 8

    Green MT, Dunkel EC, Pavan-Langston D . Effect of immunisation and immunosuppression on induced ocular shedding and recovery of herpes simplex virus in infected rabbits. Exp Eye Res 1987;45:375–83.

  9. 9

    Metcalf JF, Koga J, Chatterjee S, Whitley RJ . Passive immunization with monoclonal antibodies against herpes simplex virus glycoproteins protects mice against herpetic ocular disease. Curr Eye Res 1987;6:173–7.

  10. 10

    Lausch RN, Staats H, Oakes JE, Cohen GH, Eisenberg RJ . Prevention of herpes keratitis by monoclonal antibodies for discontinuous and continuous epitopes on glycoprotein D. Invest Ophthalmol Vis Sci 1991;32:2735–40.

  11. 11

    Inoue Y, Ohashi Y, Watanabe H, Manabe P . Protective effects of anti-glycoprotein D monoclonal antibodies in murine herpetic keratitis. Curr Eye Res 1992;11:53–60.

  12. 12

    Cappel R . Comparison of humoral and cellular immune responses after immunisation with live, UV inactivated herpes simplex and a subunit vaccine and efficacy of these immunisations. Arch Virol 1976;52:29–36.

  13. 13

    Carter CA, Hartley CE, Skinner GRB, Turner SP, Easty DL . Experimental ulcerative herpetic keratitis. IV. Preliminary observations on the efficacy of a herpes simplex subunit vaccine. Br J Ophthalmol 1981;65:679–82.

  14. 14

    Johnson DC, Ligas MW . Herpes simplex viruses lacking glycoprotein D are unable to inhibit virus penetration: quantitative evidence for virus-specific cell surface receptors. J Virol 1988;62:4605–12.

  15. 15

    Cohen GH, Dietzschold B, Ponce de Leon M, Long D, Golub E, Varrichio A, et al. Localisation and synthesis of an antigenic determinant of herpes simplex virus glycoprotein D that stimulates the production of neutralising antibody. J Virol 1984;49:102–7.

  16. 16

    Sandstrom IK, Foster CS, Wells PA, Knipe D, Caron L, Greene MI . Previous immunisation of mice with herpes simplex virus type-1 strain MP protects against secondary corneal infection. Clin Immunol Immuno pathol 1986;40:326–34.

  17. 17

    Foster CS, Sandstrom IK, Wells PA, Thompson P, Daigle J, Opremcak EM . Immunomodulation of experimental murine herpes simplex keratitis. II. Glycoprotein D protection. Curr Eye Res 1988;7:1051–61.

  18. 18

    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 Vis Sci 1990;31:411–8.

  19. 19

    Eisenberg RJ, Cerini CP, Heilman CJ, Joseph AD, Dietzschold B, Golub E, et al. Synthetic glycoprotein D related peptides protect mice against herpes simplex virus challenge. J Virol 1985;56:1014–7.

  20. 20

    Foster CS, Tsai Y, Monroe JG, Cambell RC, Cestari M, Knipe D, Greene MI . Genetic studies on murine susceptibility to herpes simplex keratitis. Clin Immunol Immunopathol 1986;40:313–25.

  21. 21

    Bernatowicz MS, Matsueda GR . Preparation of peptide protein immunogens using N-succinimidyl bromacetate as a heterobifunctional crosslinking reagent. Anal Biochem 1986;155:95–102.

  22. 22

    Ellman GL . Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70–7.

  23. 23

    Showalter SD, Zweig M, Hampar B . Monoclonal antibodies to herpes simplex virus type 1 proteins, including the immediate-early protein ICP-4. Infect Immun 1981;34:684–92.

  24. 24

    Hampar B, Zweig M, Showalter D, Bladen SV, Riggs CW . Enzyme-linked immunosorbent assay for determination of antibodies against herpes simplex virus types 1 and 2 in human. J Clin Microbiol 1985;21:496–500.

  25. 25

    Zweig M, Showalter SD, Bladen SV, Heilman CJ Jr, Hampar B . Herpes simplex virus type 2 glycoprotein gF and type 1 glycoprotein gC have related antigenic determinants. J Virol 1983;47:185–92.

  26. 26

    Eisenberg RJ, Ponce de Leon M, Pereira L, Long D, Cohen GH . Purification of glycoprotein gD of herpes simplex virus types 1 and 2 by use of monoclonal antibody. J Virol 1982;41:1099–104.

  27. 27

    Nakamura RM, Voller A, Bidwell DE . Enzyme immunoassays: heterogeneous and homogeneous systems. In: Weir DM, editor. Handbook of experimental immunology London: Blackwell Scientific Publications 1986:21–4.

  28. 28

    Thompson P, Wells PA, Sandstrom IK, Opremcak EM, Millin JA, Daigle A, Foster CS . Immunomodulation of experimental murine herpes simplex keratitis. I. UV HSV protection. Curr Eye Res 1988;7:1043–9.

  29. 29

    Sainz de la Maza M, Wells PA, Foster CS . Cyclic nucleotide modulation of herpes simplex virus latency and reactivation. Invest Ophthalmol Vis Sci 1989;30:2154–9.

  30. 30

    Schrier RD, Pizer LI, Moorhead JW . Type-specific delayed hypersensitivity and protective immunity induced by isolated herpes simplex virus glycoprotein. J Immunol 1983;130:1413–8.

  31. 31

    Wells PA, Ihley TM, Foster CS . Immunisation with a synthetic HSV-1 glycoprotein D peptide protects mice from herpes simplex keratitis (HSK). Invest Ophthalmol Vis Sci 1988;29(Suppl):–153.

  32. 32

    Watari E, Dietzschold B, Szokan G, Heber-Katz E . A synthetic peptide induces long-term protection from lethal infection with herpes simplex virus 2. J Exp Med 1987;165:459–70.

  33. 33

    Herlyn D, Koprowski H . IgG2a monoclonal antibodies inhibit human tumour growth through interaction with effector cells. Proc Natl Acad Sci USA 1982;79:4761–5.

  34. 34

    Kaminski MS, Kitamura K, Maloney DC, Campbell MJ, Levy R . Importance of antibody isotype in monoclonal antiidiotype therapy of a murine B cell lymphoma: a study of the hybridoma class switch variants. J Immunol 1986;136:1123–30.

  35. 35

    Atassi MZ, Webster RG . Localisation, synthesis, and activity of an antigenic site on influenza virus hemagglutinin. Proc Natl Acad Sci USA 1983;80:840–4.

  36. 36

    Heiligenhaus A, Berra A, Dutt JE, Zhao TZ, Wells PA, Foster CS . T-zell vermittelter Schutz gegen HSV-1 keratitis durch Immunisierung mit synthetischen Peptid des glykoprotein D. Ophthalmologe 1994;91:in press.

  37. 37

    Balachandran N, Bachetti S, Rawls WE . Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibody to five glycoproteins of herpes simplex virus type 2. Infect Immun 1982;37:1132–7.

  38. 38

    Rector JT, Lausch RN, Oakes JE . Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection. Infect Immun 1982;38:168–74.

  39. 39

    Kümel G, Kaerner HC, Levine M, Schröder CH, Glorioso JC . Passive immune protection by herpes simplex virus-specific monoclonal antibodies and monoclonal antibody-resistant mutants in pathogenicity. J Virol 1985;56:930–7.

  40. 40

    Oakes JE, Lausch RN . Monoclonal antibodies suppress replication of herpes simplex virus type 1 in trigeminal ganglia. J Virol 1984;51:656–61.

  41. 41

    Fuller AO, Spear PG . Specificities of monoclonal and polyclonal antibodies that inhibit absorption of herpes simplex virus to cells and lack of inhibition by potent neutralising antibodies. J Virol 1985;55:475–82.

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Correspondence to C S Foster.

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Keywords

  • gD peptide
  • Glycoprotein. HS+V-1. Keratitis

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