Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1997 Oct;71(10):7442–7447. doi: 10.1128/jvi.71.10.7442-7447.1997

Plasmid DNA encoding replicating foot-and-mouth disease virus genomes induces antiviral immune responses in swine.

G Ward 1, E Rieder 1, P W Mason 1
PMCID: PMC192090  PMID: 9311823

Abstract

DNA vaccine candidates for foot-and-mouth disease (FMD) were engineered to produce FMD virus (FMDV) particles that were noninfectious in cell culture or animals. The prototype plasmid, pWRM, contains a cytomegalovirus immediate-early promoter-driven genome-length type A12 cDNA followed by the bovine growth hormone polyadenylation site. BHK cells transfected with this plasmid produced virus, but the specific infectivity of pWRM was much lower than that achieved with in vitro-generated RNA genomes. To improve the infectivity of the plasmid, a cDNA encoding the hepatitis delta virus ribozyme was added to the 3' end of the FMDV cDNA. The resulting plasmid, pWRMH, exhibited slightly increased infectivity in cell culture and produced virus when inoculated into suckling mice. A third plasmid, pWRMHX, was created by removal of the sequences encoding the cell binding site found in capsid protein VP1 of pWRMH. Although cells transfected with pWRMHX produced viral capsids, this plasmid was not lethal in suckling mice, indicating that particles lacking the cell binding site were not able to initiate secondary infectious cycles. Swine inoculated with pWRMHX did not show any signs of disease and produced neutralizing antibodies to FMDV, and 20% of the vaccinated animals were protected from challenge. A derivative of pWRMHX, pWRMHX-pol-, harboring a mutation designed to inactivate the viral polymerase was much less immunogenic, indicating that immunogenicity of pWRMHX resulted, in part, from amplification of the viral genome in the animal.

Full Text

The Full Text of this article is available as a PDF (268.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bahnemann H. G. Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine. Vaccine. 1990 Aug;8(4):299–303. doi: 10.1016/0264-410X(90)90083-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beck E., Strohmaier K. Subtyping of European foot-and-mouth disease virus strains by nucleotide sequence determination. J Virol. 1987 May;61(5):1621–1629. doi: 10.1128/jvi.61.5.1621-1629.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boshart M., Weber F., Jahn G., Dorsch-Häsler K., Fleckenstein B., Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. doi: 10.1016/s0092-8674(85)80025-8. [DOI] [PubMed] [Google Scholar]
  4. Brown C. C., Piccone M. E., Mason P. W., McKenna T. S., Grubman M. J. Pathogenesis of wild-type and leaderless foot-and-mouth disease virus in cattle. J Virol. 1996 Aug;70(8):5638–5641. doi: 10.1128/jvi.70.8.5638-5641.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown F. New approaches to vaccination against foot-and-mouth disease. Vaccine. 1992;10(14):1022–1026. doi: 10.1016/0264-410x(92)90111-v. [DOI] [PubMed] [Google Scholar]
  6. Cox G. J., Zamb T. J., Babiuk L. A. Bovine herpesvirus 1: immune responses in mice and cattle injected with plasmid DNA. J Virol. 1993 Sep;67(9):5664–5667. doi: 10.1128/jvi.67.9.5664-5667.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DiMarchi R., Brooke G., Gale C., Cracknell V., Doel T., Mowat N. Protection of cattle against foot-and-mouth disease by a synthetic peptide. Science. 1986 May 2;232(4750):639–641. doi: 10.1126/science.3008333. [DOI] [PubMed] [Google Scholar]
  8. Donnelly J. J., Ulmer J. B., Liu M. A. Immunization with DNA. J Immunol Methods. 1994 Dec 2;176(2):145–152. doi: 10.1016/0022-1759(94)90308-5. [DOI] [PubMed] [Google Scholar]
  9. Dubensky T. W., Jr, Driver D. A., Polo J. M., Belli B. A., Latham E. M., Ibanez C. E., Chada S., Brumm D., Banks T. A., Mento S. J. Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer. J Virol. 1996 Jan;70(1):508–519. doi: 10.1128/jvi.70.1.508-519.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fynan E. F., Webster R. G., Fuller D. H., Haynes J. R., Santoro J. C., Robinson H. L. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11478–11482. doi: 10.1073/pnas.90.24.11478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herweijer H., Latendresse J. S., Williams P., Zhang G., Danko I., Schlesinger S., Wolff J. A. A plasmid-based self-amplifying Sindbis virus vector. Hum Gene Ther. 1995 Sep;6(9):1161–1167. doi: 10.1089/hum.1995.6.9-1161. [DOI] [PubMed] [Google Scholar]
  12. Higuchi R., Krummel B., Saiki R. K. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 1988 Aug 11;16(15):7351–7367. doi: 10.1093/nar/16.15.7351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huang Y., Carmichael G. G. Role of polyadenylation in nucleocytoplasmic transport of mRNA. Mol Cell Biol. 1996 Apr;16(4):1534–1542. doi: 10.1128/mcb.16.4.1534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jablonski S. A., Morrow C. D. Mutation of the aspartic acid residues of the GDD sequence motif of poliovirus RNA-dependent RNA polymerase results in enzymes with altered metal ion requirements for activity. J Virol. 1995 Mar;69(3):1532–1539. doi: 10.1128/jvi.69.3.1532-1539.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johanning F. W., Conry R. M., LoBuglio A. F., Wright M., Sumerel L. A., Pike M. J., Curiel D. T. A Sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expression in vivo. Nucleic Acids Res. 1995 May 11;23(9):1495–1501. doi: 10.1093/nar/23.9.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Manickan E., Karem K. L., Rouse B. T. DNA vaccines -- a modern gimmick or a boon to vaccinology? Crit Rev Immunol. 1997;17(2):139–154. doi: 10.1615/critrevimmunol.v17.i2.20. [DOI] [PubMed] [Google Scholar]
  17. Mason P. W., Piccone M. E., Mckenna T. S., Chinsangaram J., Grubman M. J. Evaluation of a live-attenuated foot-and-mouth disease virus as a vaccine candidate. Virology. 1997 Jan 6;227(1):96–102. doi: 10.1006/viro.1996.8309. [DOI] [PubMed] [Google Scholar]
  18. Mason P. W., Rieder E., Baxt B. RGD sequence of foot-and-mouth disease virus is essential for infecting cells via the natural receptor but can be bypassed by an antibody-dependent enhancement pathway. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1932–1936. doi: 10.1073/pnas.91.5.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mateu M. G., Camarero J. A., Giralt E., Andreu D., Domingo E. Direct evaluation of the immunodominance of a major antigenic site of foot-and-mouth disease virus in a natural host. Virology. 1995 Jan 10;206(1):298–306. doi: 10.1016/s0042-6822(95)80045-x. [DOI] [PubMed] [Google Scholar]
  20. McKenna T. S., Lubroth J., Rieder E., Baxt B., Mason P. W. Receptor binding site-deleted foot-and-mouth disease (FMD) virus protects cattle from FMD. J Virol. 1995 Sep;69(9):5787–5790. doi: 10.1128/jvi.69.9.5787-5790.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mulcahy G., Gale C., Robertson P., Iyisan S., DiMarchi R. D., Doel T. R. Isotype responses of infected, virus-vaccinated and peptide-vaccinated cattle to foot-and-mouth disease virus. Vaccine. 1990 Jun;8(3):249–256. doi: 10.1016/0264-410x(90)90054-p. [DOI] [PubMed] [Google Scholar]
  22. Mulcahy G., Pullen L. A., Gale C., DiMarchi R. D., Doel T. R. Mouse protection test as a predictor of the protective capacity of synthetic foot-and-mouth disease vaccines. Vaccine. 1991 Jan;9(1):19–24. doi: 10.1016/0264-410x(91)90311-s. [DOI] [PubMed] [Google Scholar]
  23. Mulcahy G., Reid E., Dimarchi R. D., Gale C., Doel T. R. Maturation of functional antibody affinity in animals immunised with synthetic foot-and-mouth disease virus. Res Vet Sci. 1992 Mar;52(2):133–140. doi: 10.1016/0034-5288(92)90001-i. [DOI] [PubMed] [Google Scholar]
  24. Perrotta A. T., Been M. D. The self-cleaving domain from the genomic RNA of hepatitis delta virus: sequence requirements and the effects of denaturant. Nucleic Acids Res. 1990 Dec 11;18(23):6821–6827. doi: 10.1093/nar/18.23.6821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Piccone M. E., Rieder E., Mason P. W., Grubman M. J. The foot-and-mouth disease virus leader proteinase gene is not required for viral replication. J Virol. 1995 Sep;69(9):5376–5382. doi: 10.1128/jvi.69.9.5376-5382.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Polo J. M., Lim B., Govindarajan S., Lai M. M. Replication of hepatitis delta virus RNA in mice after intramuscular injection of plasmid DNA. J Virol. 1995 Aug;69(8):5203–5207. doi: 10.1128/jvi.69.8.5203-5207.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Racaniello V. R., Baltimore D. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science. 1981 Nov 20;214(4523):916–919. doi: 10.1126/science.6272391. [DOI] [PubMed] [Google Scholar]
  28. Rieder E., Baxt B., Lubroth J., Mason P. W. Vaccines prepared from chimeras of foot-and-mouth disease virus (FMDV) induce neutralizing antibodies and protective immunity to multiple serotypes of FMDV. J Virol. 1994 Nov;68(11):7092–7098. doi: 10.1128/jvi.68.11.7092-7098.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rieder E., Berinstein A., Baxt B., Kang A., Mason P. W. Propagation of an attenuated virus by design: engineering a novel receptor for a noninfectious foot-and-mouth disease virus. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10428–10433. doi: 10.1073/pnas.93.19.10428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rieder E., Bunch T., Brown F., Mason P. W. Genetically engineered foot-and-mouth disease viruses with poly(C) tracts of two nucleotides are virulent in mice. J Virol. 1993 Sep;67(9):5139–5145. doi: 10.1128/jvi.67.9.5139-5145.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Robinson H. L., Hunt L. A., Webster R. G. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine. 1993;11(9):957–960. doi: 10.1016/0264-410x(93)90385-b. [DOI] [PubMed] [Google Scholar]
  32. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  33. Taboga O., Tami C., Carrillo E., Núez J. I., Rodríguez A., Saíz J. C., Blanco E., Valero M. L., Roig X., Camarero J. A. A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants. J Virol. 1997 Apr;71(4):2606–2614. doi: 10.1128/jvi.71.4.2606-2614.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ulmer J. B., Donnelly J. J., Parker S. E., Rhodes G. H., Felgner P. L., Dwarki V. J., Gromkowski S. H., Deck R. R., DeWitt C. M., Friedman A. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993 Mar 19;259(5102):1745–1749. doi: 10.1126/science.8456302. [DOI] [PubMed] [Google Scholar]
  35. Ulmer J. B., Sadoff J. C., Liu M. A. DNA vaccines. Curr Opin Immunol. 1996 Aug;8(4):531–536. doi: 10.1016/s0952-7915(96)80042-2. [DOI] [PubMed] [Google Scholar]
  36. Wang B., Ugen K. E., Srikantan V., Agadjanyan M. G., Dang K., Refaeli Y., Sato A. I., Boyer J., Williams W. V., Weiner D. B. Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4156–4160. doi: 10.1073/pnas.90.9.4156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wang K. S., Choo Q. L., Weiner A. J., Ou J. H., Najarian R. C., Thayer R. M., Mullenbach G. T., Denniston K. J., Gerin J. L., Houghton M. Structure, sequence and expression of the hepatitis delta (delta) viral genome. Nature. 1986 Oct 9;323(6088):508–514. doi: 10.1038/323508a0. [DOI] [PubMed] [Google Scholar]
  38. Wolff J. A., Malone R. W., Williams P., Chong W., Acsadi G., Jani A., Felgner P. L. Direct gene transfer into mouse muscle in vivo. Science. 1990 Mar 23;247(4949 Pt 1):1465–1468. doi: 10.1126/science.1690918. [DOI] [PubMed] [Google Scholar]
  39. Xiang Z. Q., Spitalnik S., Tran M., Wunner W. H., Cheng J., Ertl H. C. Vaccination with a plasmid vector carrying the rabies virus glycoprotein gene induces protective immunity against rabies virus. Virology. 1994 Feb 15;199(1):132–140. doi: 10.1006/viro.1994.1105. [DOI] [PubMed] [Google Scholar]
  40. Zhou X., Berglund P., Rhodes G., Parker S. E., Jondal M., Liljeström P. Self-replicating Semliki Forest virus RNA as recombinant vaccine. Vaccine. 1994 Dec;12(16):1510–1514. doi: 10.1016/0264-410x(94)90074-4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES