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
2019-12-07
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. Virology 159, 57-66.[CrossRef]
    [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 Sciences 772, 47-63.[CrossRef]
    [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 Immunology 226, 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 Research 6, 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. Virology 265, 46-56.[CrossRef]
    [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 Immunity 66, 5423-5432.
    [Google Scholar]
  7. Buddle, B. M. ( 2001; ). Vaccination of cattle against Mycobacterium bovis. Tuberculosis 81, 125-132.[CrossRef]
    [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 Therapy 1, 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 Journal 33, 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. Nature 408, 740-745.[CrossRef]
    [Google Scholar]
  11. Kamstrup, S., Verthelyi, D. & Klinman, D. M. ( 2001; ). Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotides. Veterinary Microbiology 78, 353-362.[CrossRef]
    [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 Immunology 247, 131-142.
    [Google Scholar]
  13. Krieg, A. M. ( 2000; ). Immune effects and mechanisms of action of CpG motifs. Vaccine 19, 618-622.[CrossRef]
    [Google Scholar]
  14. Krieg, A. M. & Davis, H. L. ( 2001; ). Enhancing vaccines with immune stimulatory CpG DNA. Current Opinion in Molecular Therapeutics 3, 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. Nature 374, 546-549.[CrossRef]
    [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, USA 95, 12631-12636.[CrossRef]
    [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 Microbiology 6, 23-27.[CrossRef]
    [Google Scholar]
  18. Laemmli, U. K. ( 1970; ). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.[CrossRef]
    [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 Virology 74, 6077-6086.[CrossRef]
    [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 Virology 82, 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. Virology 289, 327-333.[CrossRef]
    [Google Scholar]
  22. McCluskie, M. J., Weeratna, R. D. & Davis, H. L. ( 2000; ). The role of CpG in DNA vaccines. Springer Seminars in Immunopathology 22, 125-132.[CrossRef]
    [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 Immunopathology 84, 43-59.[CrossRef]
    [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 Virology 81, 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 Development 11, 333-340.[CrossRef]
    [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. Vaccine 20, 3014-3022.[CrossRef]
    [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 Virology 80, 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. Vaccine 19, 764-778.[CrossRef]
    [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. Science 273, 352-354.[CrossRef]
    [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 Biology 10, 1139-1142.[CrossRef]
    [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 Biology 70, 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 Virology 69, 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 Record 262, 186-192.[CrossRef]
    [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 Immunology 214, 155-164.[CrossRef]
    [Google Scholar]
  35. van Drunen Littel-van den Hurk, S. & Babiuk, L. A. ( 1986; ). Synthesis and processing of bovine herpesvirus 1 glycoproteins. Journal of Virology 59, 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. Virology 135, 466-479.[CrossRef]
    [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. Vaccine 8, 358-368.[CrossRef]
    [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. Vaccine 11, 25-35.[CrossRef]
    [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. Vaccine 12, 1295-1302.[CrossRef]
    [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. Vaccine 15, 36-44.[CrossRef]
    [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 Virology 79, 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. Virology 260, 35-46.[CrossRef]
    [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 Reviews 43, 13-28.[CrossRef]
    [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. Vaccine 19, 2474-2479.[CrossRef]
    [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 Virology 70, 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 Medicine 46, 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

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