1887

Abstract

The potential of CpG-enhanced plasmid DNA vectors encoding a truncated secreted form of bovine herpesvirus-1 (BHV-1) glycoprotein D (tgD) to induce enhanced immune responses in cattle was investigated. We created tgD expression plasmids containing 0, 40 or 88 copies of the hexamer 5′ GTCGTT 3′, a known pan-activating CpG motif in several species. The total tgD-specific IgG titre of calves immunized with these plasmids did not correlate with the CpG content of the plasmid backbone. However, the pBISIA88-tgD-vaccinated group showed a significantly lower IgG1:IgG2 ratio than calves immunized with pBISIA40-tgD or pMASIA-tgD, which has no CpG motifs inserted. Antigen-specific lymphocyte proliferation and IFN-γ secretion by peripheral blood mononuclear cells correlated positively with the CpG content of the vectors. In contrast, calves that received a killed BHV-1 vaccine had an IgG1-predominant isotype and low lymphocyte proliferation and IFN-γ levels. Following challenge, the pBISIA88-tgD-immunized group developed the greatest anamnestic response, the highest BHV-1 neutralization titres in serum and a significantly lower level of virus shedding than the saline control group. However, there were no significant differences in clinical symptoms of infection between the DNA-immunized groups and the saline control group. These data indicate that CpG-enhanced plasmids induce augmented immune responses and could be used to vaccinate against pathogens requiring a strong cellular response for protection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-12-2973
2002-12-01
2020-09-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/12/0832973a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-12-2973&mimeType=html&fmt=ahah

References

  1. Babiuk L. A., L’Italien J., van Drunen Littel-van den Hurk S., Zamb T., Lawman J. P., Hughes G., Gifford G. A.. 1987; Protection of cattle from bovine herpesvirus type 1 (BHV-1) infection by immunization with individual viral glycoproteins. Virology159:57–66
    [Google Scholar]
  2. Babiuk L. A., Lewis P. J., Cox G., van Drunen Littel-van den Hurk S., Baca-Estrada M., Tikoo S. K.. 1995; DNA immunization with bovine herpesvirus-1 genes. Annals of the New York Academy of Sciences772:47–63
    [Google Scholar]
  3. Babiuk L. A., Lewis P. J., van Drunen Littel-van den Hurk S., Tikoo S., Liang X.. 1998; Nucleic acid vaccines: veterinary applications. Current Topics in Microbiology and Immunology226:90–106
    [Google Scholar]
  4. Braun R., Babiuk L., van Drunen Littel-van den Hurk S.. 1997; Enhanced immune response to an intradermally delivered DNA vaccine expressing a secreted form of BHV-1 gD. Vaccine Research6:151–164
    [Google Scholar]
  5. Braun R. P., Babiuk L. A., Loehr B. I., van Drunen Littel-van den Hurk S.. 1999; Particle-mediated DNA immunization of cattle confers long-lasting immunity against bovine herpesvirus-1. Virology265:46–56
    [Google Scholar]
  6. Brown W. C., Estes D. M., Chantler S. E., Kegerreis K. A., Suarez C. E.. 1998; DNA and a CpG oligonucleotide derived from Babesia bovis are mitogenic for bovine B cells. Infection and Immunity66:5423–5432
    [Google Scholar]
  7. Buddle B. M.. 2001; Vaccination of cattle against Mycobacterium bovis . Tuberculosis81:125–132
    [Google Scholar]
  8. Cotten M., Baker A., Saltik M., Wagner E., Buschle M.. 1994; Lipopolysaccharide is a frequent contaminant of plasmid DNA preparations and can be toxic to primary human cells in the presence of adenovirus. Gene Therapy1:239–246
    [Google Scholar]
  9. Harland R. J., Potter A. A., van Drunen Littel-van den Hurk S., van Donkersgoed J., Parker M. D., Zamb T. J., Janzen E. D.. 1992; The effect of subunit or modified live herpesvirus-1 vaccines on the efficacy of a recombinant Pasteurella haemolytica vaccine for the prevention of respiratory disease in feedlot calves. Canadian Veterinary Journal33:734–741
    [Google Scholar]
  10. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., Akira S.. 2000; A Toll-like receptor recognizes bacterial DNA. Nature408:740–745
    [Google Scholar]
  11. Kamstrup S., Verthelyi D., Klinman D. M.. 2001; Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotides. Veterinary Microbiology78:353–362
    [Google Scholar]
  12. Klinman D. M., Ishii K. J., Verthelyi D.. 2000; CpG DNA augments the immunogenicity of plasmid DNA vaccines. Current Topics in Microbiology and Immunology247:131–142
    [Google Scholar]
  13. Krieg A. M.. 2000; Immune effects and mechanisms of action of CpG motifs. Vaccine19:618–622
    [Google Scholar]
  14. Krieg A. M., Davis H. L.. 2001; Enhancing vaccines with immune stimulatory CpG DNA. Current Opinion in Molecular Therapeutics3:15–24
    [Google Scholar]
  15. Krieg A. M., Yi A. K., Matson S., Waldschmidt T. J., Bishop G. A., Teasdale R., Koretzky G. A., Klinman D. M.. 1995; CpG motifs in bacterial DNA trigger direct B-cell activation. Nature374:546–549
    [Google Scholar]
  16. Krieg A. M., Wu T., Weeratna R., Efler S. M., Love-Homan L., Yang L., Yi A. K., Short D., Davis H. L.. 1998a; Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proceedings of the National Academy of Sciences, USA95:12631–12636
    [Google Scholar]
  17. Krieg A. M., Yi A. K., Schorr J., Davis H. L.. 1998b; The role of CpG dinucleotides in DNA vaccines. Trends in Microbiology6:23–27
    [Google Scholar]
  18. Laemmli U. K.. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680–685
    [Google Scholar]
  19. Loehr B. I., Willson P., Babiuk L. A., van Drunen Littel-van den Hurk S.. 2000; Gene gun-mediated DNA immunization primes development of mucosal immunity against bovine herpesvirus 1 in cattle. Journal of Virology74:6077–6086
    [Google Scholar]
  20. Loehr B. I., Pontarollo R., Rankin R., Latimer L., Willson P., Babiuk L. A., van Drunen Littel-van den Hurk S.. 2001a; Priming by DNA immunization augments T-cell responses induced by modified live bovine herpesvirus vaccine. Journal of General Virology82:3035–3043
    [Google Scholar]
  21. Loehr B. I., Rankin R., Pontarollo R., King T., Willson P., Babiuk L. A., van Drunen Littel-van den Hurk S.. 2001b; Suppository-mediated DNA immunization induces mucosal immunity against bovine herpesvirus-1 in cattle. Virology289:327–333
    [Google Scholar]
  22. McCluskie M. J., Weeratna R. D., Davis H. L.. 2000; The role of CpG in DNA vaccines. Springer Seminars in Immunopathology22:125–132
    [Google Scholar]
  23. Pontarollo R. A., Rankin R., Babiuk L. A., Godson D. L., Griebel P. J., Hecker R., Krieg A. M., van Drunen Littel-van den Hurk S.. 2002; Monocytes are required for optimum in vitro stimulation of bovine peripheral blood mononuclear cells by non-methylated CpG motifs. Veterinary Immunology and Immunopathology84:43–59
    [Google Scholar]
  24. Raggo C., Habermehl M., Babiuk L. A., Griebel P.. 2000; The in vivo effects of recombinant bovine herpesvirus-1 expressing bovine interferon-γ. Journal of General Virology81:2665–2673
    [Google Scholar]
  25. Rankin R., Pontarollo R., Ioannou X., Krieg A. M., Hecker R., Babiuk L. A., van Drunen Littel-van den Hurk S.. 2001; CpG motif identification for veterinary and laboratory species demonstrates that sequence recognition is highly conserved. Antisense and Nucleic Acid Drug Development11:333–340
    [Google Scholar]
  26. Rankin R., Pontarollo R., Gomis S., Karvonen B., Willson P., Loehr B. I., Godson D. L., Babiuk L. A., Hecker R., van Drunen Littel-van den Hurk S.. 2002; CpG-containing oligodeoxynucleotides augment and switch the immune response of cattle to bovine herpesvirus-1 glycoprotein D. Vaccine20:3014–3022
    [Google Scholar]
  27. Rhodes S. G., Cocksedge J. M., Collins R. A., Morrison W. I.. 1999; Differential cytokine responses of CD4+ and CD8+ T cells in response to bovine viral diarrhoea virus in cattle. Journal of General Virology80:1673–1679
    [Google Scholar]
  28. Roy M. J., Wu M. S., Barr L. J., Fuller J. T., Tussey L. G., Speller S., Culp J., Burkholder J. K., Swain W. F., Dixon R. M., Widera G., Vessey R., King A., Ogg G., Gallimore A., Haynes J. R., Heydenburg Fuller D.. 2000; Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine. Vaccine19:764–778
    [Google Scholar]
  29. Sato Y., Roman M., Tighe H., Lee D., Corr M., Nguyen M. D., Silverman G. J., Lotz M., Carson D. A., Raz E.. 1996; Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science273:352–354
    [Google Scholar]
  30. Schnare M., Holt A. C., Takeda K., Akira S., Medzhitov R.. 2000; Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Current Biology10:1139–1142
    [Google Scholar]
  31. Shoda L. K., Kegerreis K. A., Suarez C. E., Mwangi W., Knowles D. P., Brown W. C.. 2001; Immunostimulatory CpG-modified plasmid DNA enhances IL-12, TNF-alpha, and NO production by bovine macrophages. Journal of Leukocyte Biology70:103–112
    [Google Scholar]
  32. Taylor G., Thomas L. H., Wyld S. G., Furze J., Sopp P., Howard C. J.. 1995; Role of T-lymphocyte subsets in recovery from respiratory syncytial virus infection in calves. Journal of Virology69:6658–6664
    [Google Scholar]
  33. Uwiera R. R. E., Rankin R., Adams G. P., Pontarollo R. A., van Drunen Littel-van den Hurk S., Middleton D. M., Babiuk L. A., Griebel P. J.. 2001a; Effects of intradermally administered plasmid deoxyribonucleic acid on ovine popliteal lymph node morphology. Anatomical Record262:186–192
    [Google Scholar]
  34. Uwiera R. R. E., Gerdts V., Pontarollo R. A., Babiuk L. A., Middleton D. M., Griebel P. J.. 2001b; Plasmid DNA induces increased lymphocyte trafficking: a specific role for CpG motifs. Cellular Immunology214:155–164
    [Google Scholar]
  35. van Drunen Littel-van den Hurk S., Babiuk L. A.. 1986; Synthesis and processing of bovine herpesvirus 1 glycoproteins. Journal of Virology59:401–410
    [Google Scholar]
  36. van Drunen Littel-van den Hurk S., van den Hurk J. V., Gilchrist J. E., Misra V., Babiuk L. A.. 1984; Interactions of monoclonal antibodies and bovine herpesvirus type 1 (BHV-1) glycoproteins: characterization of their biochemical and immunological properties. Virology135:466–479
    [Google Scholar]
  37. van Drunen Littel-van den Hurk S., Gifford G. A., Babiuk L. A.. 1990; Epitope specificity of the protective immune response induced by individual bovine herpesvirus-1 glycoproteins. Vaccine8:358–368
    [Google Scholar]
  38. van Drunen Littel-van den Hurk S., Parker M. D., Massie B., van den Hurk J. V., Harland R., Babiuk L. A., Zamb T. J.. 1993; Protection of cattle from BHV-1 infection by immunization with recombinant glycoprotein gIV. Vaccine11:25–35
    [Google Scholar]
  39. van Drunen Littel-van den Hurk S., van Donkersgoed J., Kowalski J., van den Hurk J. V., Harland R., Babiuk L. A., Zamb T. J.. 1994; A subunit gIV vaccine, produced by transfected mammalian cells in culture, induces mucosal immunity against bovine herpesvirus-1 in cattle. Vaccine12:1295–1302
    [Google Scholar]
  40. van Drunen Littel-van den Hurk S., Tikoo S. K., van den Hurk J. V., Babiuk L. A., van Donkersgoed J.. 1997; Protective immunity in cattle following vaccination with conventional and marker bovine herpesvirus-1 (BHV1) vaccines. Vaccine15:36–44
    [Google Scholar]
  41. van Drunen Littel-van den Hurk S., Braun R., Lewis P., Karvonen B., Baca-Estrada M., Snider M., McCartney D., Watts T., Babiuk L.. 1998; Intradermal immunization with a bovine herpesvirus-1 DNA vaccine induces protective immunity in cattle. Journal of General Virology79:831–839
    [Google Scholar]
  42. van Drunen Littel-van den Hurk S., Braun R. P., Karvonen B. C., King T., Yoo D., Babiuk L. A.. 1999; Immune responses and protection induced by DNA vaccines encoding bovine parainfluenza virus type 3 glycoproteins. Virology260:35–46
    [Google Scholar]
  43. van Drunen Littel-van den Hurk S., Gerdts V., Loehr B. I., Pontarollo R., Rankin R., Uwiera R., Babiuk L. A.. 2000; Recent advances in the use of DNA vaccines for the treatment of diseases of farmed animals. Advanced Drug Delivery Reviews43:13–28
    [Google Scholar]
  44. van Drunen Littel-van den Hurk S., Loehr B. I., Babiuk L. A.. 2001; Immunization of livestock with DNA vaccines: current studies and future prospects. Vaccine19:2474–2479
    [Google Scholar]
  45. Whitbeck J. C., Knapp A. C., Enquist L. W., Lawrence W. C., Bello L. J.. 1996; Synthesis, processing, and oligomerization of bovine herpesvirus 1 gE and gI membrane proteins. Journal of Virology70:7878–7884
    [Google Scholar]
  46. Yates W. D.. 1982; A review of infectious bovine rhinotracheitis, shipping fever pneumonia and viral–bacterial synergism in respiratory disease of cattle. Canadian Journal of Comparative Medicine46:225–263
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-12-2973
Loading
/content/journal/jgv/10.1099/0022-1317-83-12-2973
Loading

Data & Media loading...

Most cited this month 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