Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 73, Issue 9

Vaccination by cholera toxin conjugated to a herpes simplex virus type 2 glycoprotein D peptide No Access

Abstract

Immunization of BALB/cJ mice with a peptide corresponding to residues 1 to 23 of glycoprotein D [gD(1–23)] from herpes simplex virus type 2 (HSV-2) elicits antibody responses which correlate with protection against lethal HSV-2 infection. In the present study, we examined the ability of cholera toxin (CTX) to act as an immunogenic carrier for gD(1–23). The number of gD(1–23) residues conjugated to CTX affected its binding to GM ganglioside and physiological toxicity, both of which are factors affecting oral immunogenicity. The antibody response elicited after intraperitoneal (i.p.) immunization with the CTX-gD(1–23) conjugate was protective against a lethal i.p. challenge with HSV-2. In other experiments, mice were immunized i.p. on day 0 and subsequent immunizations conducted on days 14 and 28 were administered either intragastrically or intravaginally (i.vag.). Intraperitoneal priming followed by either i.p. or intragastric boosting resulted in anti-HSV-2 antibodies in vaginal washings and in protection against a lethal i.vag. challenge with HSV-2. Intraperitoneal priming followed by i.vag. boosting did not elicit anti-HSV-2 antibodies in vaginal washings and did not protect mice against a lethal i.vag. challenge with HSV-2. These results suggest that CTX can act as a systemic and an oral delivery molecule for the covalently linked gD(1–23) peptide and that such conjugates can elicit protective immune responses against systemic and genital HSV-2 infection.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1992
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-9-2357
1992-09-01
2025-05-13
Loading full text...

Full text loading...

References

  1. Ackermann M., Longnecker R., Roizman B., Pereira L. 1986; Identification, properties, and gene location of a novel glycoprotein specified by herpes simplex virus 1. Virology 150:207–220
     [Google Scholar]
  2. Balachandran N., Bacchetti S., Rawls W. E. 1982; Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infection and Immunity 37:1132–1137
     [Google Scholar]
  3. Batty I., Warrack G. H. 1955; Local antibody production in the mammary gland, spleen, uterus, vagina and appendix of the rabbit. Journal of Pathology and Bacteriology 70:335–355
     [Google Scholar]
  4. Beer A. E., Heaves W. B. 1978; Antigenic status of semen from the viewpoints of the female and the male. Fertility and Sterility 29:3–22
     [Google Scholar]
  5. Berman P. W., Vogt P. E., Gregory T., Lasky L. A., Kern E. R. 1988; Efficacy of recombinant glycoprotein D subunit vaccines on the development of primary, recurrent, and latent genital infections with herpes simplex virus type 2 in guinea pigs. Journal of Infectious Disease 157:897–902
     [Google Scholar]
  6. Brynestad K., Babbitt B., Huang L., Rouse B. T. 1990; Influence of peptide acylation on the immunogenicity of a 1-23 peptide of glycoprotein D of herpes simplex virus: implications for subunit vaccines. Journal of Virology 64:680–685
     [Google Scholar]
  7. Buckmaster E. A., Gompels U., Minson A. C. 1984; Characterization and physical mapping of an HSV-1 glycoprotein of approximately 115 × 103 molecular weight. Virology 139:408–413
     [Google Scholar]
  8. Chipperfield E. J., Evans B. A. 1972; The influence of local infection on immunoglobulin formation in the human endocervix. Clinical and Experimental Immunology 11:219–233
     [Google Scholar]
  9. Clarke D. N. 1984; Detection of antispermatozoal antibodies of IgG, IgA and IgM immunoglobulin classes in cervical mucus. American Journal of Reproductive Immunology 6:195–197
     [Google Scholar]
  10. Cohen G. H., Dietzschold B., Ponce de Leon M., Long D., Golub E., Varrichio A., Pereira L., Eisenberg R. J. 1984; Localization and synthesis of an antigenic determinant of herpes simplex glycoprotein D that stimulates production of neutralizing antibody. Journal of Virology 49:102–107
     [Google Scholar]
  11. Corey L., Spear P. G. 1986; Infections with herpes simplex viruses (parts 1 and 2). New England Journal of Medicine 314:686–691 749–757
    [Google Scholar]
  12. Craig J. P. 1971; Cholera toxin. In Microbial Toxins vol 2A p. 189. Edited by Kadis S., Montie T. C., Ajl S. J. New York: Academic Press;
     [Google Scholar]
  13. Czerkinsky C., Nilsson L.-A., Nygren H., Ouchterlony O., Tarkowski A. 1987; IgA antibody-producing cells after antigen ingestion: evidence for a common mucosal immune system in humans. Proceedings of the National Academy of Sciences, U.S.A. 84:2449–2453
     [Google Scholar]
  14. Czerkinsky C., Russell M. W., Lycke N., Lindblad M., Holmgren J. 1989; Oral administration of a Streptococcus antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues. Infection and Immunity 57:1072–1077
     [Google Scholar]
  15. Drew M. D., Owen B. D. 1988; The provision of passive immunity to colostrum-deprived piglets by bovine or porcine serum immunoglobulins. Canadian Journal of Animal Science 68:1277–1284
     [Google Scholar]
  16. Eisenberg R. J., Long D., Hogue-Angeletti R., Cohen G. H. 1984; Amino-terminal sequence of glycoprotein D of herpes simplex virus types 1 and 2. Journal of Virology 49:265–268
     [Google Scholar]
  17. Elson C. O., Ealding W. 1984; Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. Journal of Immunology 133:2892–2898
     [Google Scholar]
  18. Elson C. O., Ealding W., Lefkowitz J. 1984; A lavage technique allowing repeated measurement of IgA antibody in mouse intestinal secretions. Journal of Immunological Methods 61:101–106
     [Google Scholar]
  19. Engler H., Zawatzky R., Goldbach A., Schrӧder C. H., Weyand C., Hӓmmerling G. J., Kirchner H. 1981; Experimental infection of inbred mice with herpes simplex virus. II. Interferon production and activation of natural killer cells in the peritoneal exudate. Journal of General Virology 55:25–30
     [Google Scholar]
  20. Feenstra V., Hodaie M., Johnson D. C. 1990; Deletions in herpes simplex virus glycoprotein D define non essential and essential domains. Journal of Virology 64:2096–2102
     [Google Scholar]
  21. Geerligs H. J., Weijer W. J., Welling G. W., Welling-Wester S. 1989; The influence of different adjuvants on the immune response to a synthetic peptide comprising amino acid residues 9-21 of herpes simplex virus type 1 glycoprotein D. Journal of Immunological Methods 124:95–102
     [Google Scholar]
  22. Heber-Katz E., Hollosi M., Dietzschold B., Hudecz F., Fasman G. D. 1985; The T cell response to the glycoprotein D of the herpes simplex virus: the significance of antigen conformation. Journal of Immunology 135:1385–1390
     [Google Scholar]
  23. Holmgren J. 1981; Action of cholera toxin and the prevention and treatment of cholera. Nature, London 292:413–417
     [Google Scholar]
  24. Jackson G. D. F., Lemaitre-Coelho I., Vaerman J.-P., Bazin H., Beckers A. 1978; Rapid disappearance from serum of intravenously injected rat myeloma IgA and its secretion into bile. European Journal of Immunology 8:123–126
     [Google Scholar]
  25. Johnson D. C., Burke R. L., Gregory T. 1990; Soluble forms of herpes simplex virus glycoprotein D bind to a limited number of cell surface receptors and inhibit virus entry into cells. Journal of Virology 64:2569–2576
     [Google Scholar]
  26. Kerr W. R., Robertson M. 1953; Active and passive sensitization of the uterus of the cow in vivo against Trichomonas fetus antigen and evidence for the local production of antibody in that site. Journal of Hygiene 51:405–415
     [Google Scholar]
  27. Kikuta K., Hirabayashi Y., Nagamine T., Aizawa C., Ueno Y., Oya A., Kurata T., Tamura S.-I. 1990; Cross-protection against influenza B type virus infection by intranasal inoculation of the HA vaccines combined with cholera toxin B subunit. Vaccine 8:595–599
     [Google Scholar]
  28. Kutteh W. H., Hatch K. D., Blackwell R. E., Mestecky J. 1988; Secretory immune system of the female reproductive tract. I. Immunoglobulin and secretory component-containing cells. Obstetrics and Gynecology 71:56–60
     [Google Scholar]
  29. Larsen H. S., Russell R. G., Rouse B. T. 1983; Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes. Infection and Immunity 41:197–204
     [Google Scholar]
  30. Lebman D. A., Fuhrman J. A., Cebra J. J. 1988; Intraduodenal application of cholera holotoxin increases the potential of clones from Peyer’s patch B cells of relevant and unrelated specificities to secrete IgG and IgA. Regional Immunology 1:32–40
     [Google Scholar]
  31. Liang X., Lamm M. E., Nedrud J. G. 1988; Oral administration of cholera toxin-Sendai virus conjugate potentiates gut and respiratory immunity against Sendai virus. Journal of Immunology 141:1495–1501
     [Google Scholar]
  32. Liang X., Lamm M. E., Nedrud J. G. 1989; Cholera toxin as a mucosal adjuvant: glutaraldehyde treatment dissociated adjuvanti-city from toxicity. Journal of Immunology 143:484–490
     [Google Scholar]
  33. Ligas M. W., Johnson D. C. 1988; A herpes simplex virus mutant in which glycoprotein D sequences are replaced by /1-galactosidase sequences binds to but is unable to penetrate into cells. Journal of Virology 62:1486–1494
     [Google Scholar]
  34. Longnecker R., Chatterjee S., Whitley R. J., Roizman B. 1987; Identification of a herpes simplex virus 1 glycoprotein gene within a gene cluster dispensable for growth in cell culture. Proceedings of the National Academy of Sciences, U.S.A. 84:4303–4307
     [Google Scholar]
  35. Lycke N. 1986; A sensitive method for the detection of specific antibody production in different isotypes from single lamina propria plasma cells. Scandinavian Journal of Immunology 24:393–403
     [Google Scholar]
  36. Lycke N., Holmgren J. 1986; Strong adjuvant properties of cholera toxin in gut mucosal immune responses to orally presented antigens. Immunology 59:301–308
     [Google Scholar]
  37. McDermott M. R., Bienenstock J. 1979; Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory and genital tissues. Journal of Immunology 122:1892–1898
     [Google Scholar]
  38. McDermott M. R., Clark D. A., Bienenstock J. 1980; Evidence for a common mucosal immunologic system. II. Influence of the oestrous cycle on B immunoblast migration into genital and intestinal tissues. Journal of Immunology 124:2536–2539
     [Google Scholar]
  39. McDermott M. R., Smiley J. R., Brais P. L. J., Rudzroga H. E., Bienenstock J. 1984; Immunity in the female genital tract after intravaginal vaccination of mice with an attenuated strain of herpes simplex virus type 2. Journal of Virology 51:747–753
     [Google Scholar]
  40. McDermott M. R., Brais P. L. J., Goettshe G., Evelegh M. J. 1987; Expression of immunity to intravaginal herpes simplex virus type 2 infection in the genital tract and associated lymph nodes. Archives of Virology 93:51–68
     [Google Scholar]
  41. McDermott M. R., Goldsmith C. H., Rosenthal K. L., Brais L. J. 1989; T. lymphocytes in genital lymph nodes protect mice from intravaginal infection with herpes simplex virus type 2. Journal of Infectious Diseases 159:460–466
     [Google Scholar]
  42. McDermott M. R., Brais L. J., Evelegh M. J. 1990; Mucosal and systemic antiviral antibodies in mice inoculated intravaginally with herpes simplex virus type 2. Journal of General Virology 71:1497–1504
     [Google Scholar]
  43. McKenzie S. J., Halsey J. F. 1984; Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response. Journal of Immunology 133:1818–1824
     [Google Scholar]
  44. Marsden H. S., Buckmaster A., Palfreyman J., Hope R. G., Minson A. C. 1984; Characterization of the 92000 dalton glycoprotein induced by HSV type 2. Journal of Virology 50:547–554
     [Google Scholar]
  45. Martin S., Moss B., Berman P. W., Laskey L. A., Rouse B. T. 1987; Mechanisms of antiviral immunity induced by a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: cytotoxic T cells. Journal of Virology 61:726–734
     [Google Scholar]
  46. Melnick J. L. 1978; Advantages and disadvantages of killed and live poliomyelitis vaccines. Bulletin of the World Health Organization 56:21–38
     [Google Scholar]
  47. Mendis L. N., Best J. M., Banatvala J. G. 1981; Class-specific antibodies (IgG and IgA) to membrane antigens of herpes simplex type-2 infected cells in patients with cervical dysplasia and neoplasia. International Journal of Cancer 27:669–677
     [Google Scholar]
  48. Merrinran H., Woods S., Winter C., Fahnlander A., Corey L. 1984; Secretory IgA antibody in cervicovaginal secretions from women with genital infection due to herpes simplex virus. Journal of Infectious Disease 149:505–510
     [Google Scholar]
  49. Mestecky J. 1987; The common mucosal immune system and current strategies for induction of immune response in external secretions. Journal of Clinical Immunology 7:265–269
     [Google Scholar]
  50. Mestecky J., McGhee J. R., Arnold R. R., Michalek S. M., Prince S. J., Babb J. L. 1978; Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. Journal of Clinical Investigation 61:731–737
     [Google Scholar]
  51. Morahan P. S., Morse S. S., McGeorge M. B. 1980; Macrophage extrinsic antiviral activity during herpes simplex virus infection. Journal of General Virology 46:291–300
     [Google Scholar]
  52. Nichols R. L., Murray E. S., Nisson P. E. 1978; Use of enteric vaccines in protection against chlamydial infections of the genital tract and the eye of guinea pigs. Journal of Infectious Disease 138:742–746
     [Google Scholar]
  53. Ogra P. L., Ogra S. S. 1973; Local antibody response to poliovaccine in the human female genital tract. Journal of Immunology 110:1307–1311
     [Google Scholar]
  54. Parr E. L., Parr M. B. 1990; A comparison of antibody titres in mouse uterine fluid after immunization by several routes, and the effect of the uterus on antibody titres in vaginal fluid. Journal of Reproduction and Fertility 89:619–625
     [Google Scholar]
  55. Parr E. L., Parr M. B., Thapar M. 1988; A comparison of specific antibody responses in mouse vaginal fluid after immunization by several routes. Journal of Reproductive Immunology 14:165–176
     [Google Scholar]
  56. Parr M. B., Parr E. L. 1989; Immunohistochemical investigation of secretory component and immunoglobulin A in the genital tract of the female rat. Journal of Reproduction and Fertility 85:105–113
     [Google Scholar]
  57. Pierce N. F., Gowans J. L. 1975; Cellular kinetics of the intestinal immune response to cholera toxoid in rats. Journal of Experimental Medicine 142:1550–1563
     [Google Scholar]
  58. Plaeger-Marshall S., Wilson L. A., Smith J. W. 1983; Alteration of rabbit alveolar and peritoneal macrophage function by herpes simplex virus. Infection and Immunity 41:1376–1379
     [Google Scholar]
  59. Rawls W. E. 1985; Herpes simplex virus. In Virology pp 527–561 Edited by Fields B. N. New York: Academic Press;
     [Google Scholar]
  60. Rebello R., Green F. H. Y., Fox H. 1975; A study of the secretory immune system of the female reproductive tract. British Journal of Obstetrics and Gynaecology 82:812–816
     [Google Scholar]
  61. Richman D. D., Buckmaster A., Bell S., Hodgman C., Minson A. C. 1986; Identification of a new glycoprotein of herpes simplex virus type 1 and genetic mapping of the gene that codes for it. Journal of Virology 57:647–655
     [Google Scholar]
  62. Roizman B., Norrild B., Chan C., Pereira L. 1984; Identification and primary mapping with monoclonal antibodies of a herpes simplex virus 2 glycoprotein lacking a known type 1 counterpart. Virology 133:242–247
     [Google Scholar]
  63. Rosenthall K. L., Smiley J. R., South S., Johnson D. C. 1987; Cells expressing herpes simplex virus glycoprotein gC but not gG, gD or gE are recognized by murine virus-specific cytotoxic T lymphocytes. Journal of Virology 61:2438–2447
     [Google Scholar]
  64. SAS Institute 1985; General linear models. In SAS User’s Guide: Statistics pp 140–199 Cary: SAS Institute;
     [Google Scholar]
  65. Sheldrake R. F., Husband A. J., Watson D. L., Cripps A. W. 1984; Selective transport of serum-derived IgA into mucosal secretions. Journal of Immunology 132:363–368
     [Google Scholar]
  66. Shore S. L., Cromeans T. L., Norrild B. 1979; Early damage of herpes-infected cells by antibody dependent cellular cytotoxicity: relative roles of virus-specified cell surface antigen and input virus. Journal of Immunology 123:2239–2244
     [Google Scholar]
  67. Simmons A., Nash A. A. 1985; Role of antibody in primary and recurrent herpes simplex virus infection. Journal of Virology 53:944–948
     [Google Scholar]
  68. Spear P. G. 1984; Glycoproteins specified by herpes simplex virus. In The Herpesviruses vol 3 pp 315–357 Edited by Roizman B. New York: Plenum Press;
     [Google Scholar]
  69. Stanberry L. R., Bernstein D. I., Burke R. L., Pachl C., Myers M. G. 1987; Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes. Journal of Infectious Diseases 155:914–920
     [Google Scholar]
  70. Steinecker F., Kreuter J., Lower J. 1991; High antibody titers in mice with polymethylmethacrylate nanoparticles as adjuvant for HIV vaccines. AIDS 5:431–135
     [Google Scholar]
  71. Tamura S.-I., Samegai Y., Kurata H., Kikuta K., Nagamine T., Aizawa C., Kurata T. 1989; Enhancement of protective antibody responses by cholera toxin B subunit inoculated intranasally with influenza vaccine. Vaccine 7:257–261
     [Google Scholar]
  72. Thapar M. A., Parr E. L., Parr M. B. 1990a; Secretory immune responses in mouse vaginal fluid after pelvic, parenteral or vaginal immunization. Immunology 70:121–125
     [Google Scholar]
  73. Thapar M. A., Parr E. L., Parr M. B. 1990b; The effect of adjuvants on antibody titers in mouse vaginal fluid after intravaginal immunization. Journal of Reproductive Immunology 17:207–216
     [Google Scholar]
  74. Tourville D. R., Ogra S. S., Lippes J., Tomasi T. B. 1970; The human female reproductive tract: immunohistological localization of tA, tG, tM, secretory ‘piece,’ and lactoferrin. American Journal of Obstetrics and Gynecology 108:1102–1108
     [Google Scholar]
  75. Underdown B. J., Schiff J. M. 1986; Immunoglobulin A: strategic defense initiative at the mucosal surface. Annual Review of Immunology 4:389–417
     [Google Scholar]
  76. Waldman R. H., Cruz J. M., Rowe D. S. 1971; Immunoglobulin levels and antibody to Candida albicans in human cervicovaginal secretions. Clinical and Experimental Immunology 10:427–434
     [Google Scholar]
  77. Walz M. A., Price R. W., Notkins A. L. 1974; Latent ganglionic infection with herpes simplex virus types 1 and 2: viral reactivation in vivo after neurectomy. Science 184:1175–1187
     [Google Scholar]
  78. Watari E., Dietzschold B., Szokan G., Heber-Katz E. 1987; A synthetic peptide induces long-term protection from lethal infection with herpes simplex virus 2. Journal of Experimental Medicine 165:459–466
     [Google Scholar]
  79. Weisz-Carrington P., Roux M. E., McWilliams M., Phillips-Quagliata J. M., Lamm M. E. 1979; Organ and isotype distribution of plasma cells producing specific antibody after oral immunization: evidence for a generalized secretory immune system. Journal of Immunology 123:1705–1708
     [Google Scholar]
  80. Yang S.-L., Schumacher G. F. B. 1979; Immune response after vaginal application of antigens in the rhesus monkey. Fertility and Sterility 32:588–598
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-73-9-2357
Loading
Vaccination by cholera toxin conjugated to a herpes simplex virus type 2 glycoprotein D peptide
J. Gen. Virol. 73, 2357 (1992); https://doi.org/10.1099/0022-1317-73-9-2357
/content/journal/jgv/10.1099/0022-1317-73-9-2357
/content/journal/jgv/10.1099/0022-1317-73-9-2357
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error