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. 1997 Dec;71(12):9563–9569. doi: 10.1128/jvi.71.12.9563-9569.1997

Naked DNA vaccines expressing the prM and E genes of Russian spring summer encephalitis virus and Central European encephalitis virus protect mice from homologous and heterologous challenge.

C Schmaljohn 1, L Vanderzanden 1, M Bray 1, D Custer 1, B Meyer 1, D Li 1, C Rossi 1, D Fuller 1, J Fuller 1, J Haynes 1, J Huggins 1
PMCID: PMC230264  PMID: 9371620

Abstract

Naked DNA vaccines expressing the prM and E genes of two tick-borne flaviviruses, Russian spring summer encephalitis (RSSE) virus and Central European encephalitis (CEE) virus were evaluated in mice. The vaccines were administered by particle bombardment of DNA-coated gold beads by Accell gene gun inoculation. Two immunizations of 0.5 to 1 microg of RSSE or CEE constructs/dose, delivered at 4-week intervals, elicited cross-reactive antibodies detectable by enzyme-linked immunosorbent assay and high-titer neutralizing antibodies to CEE virus. Cross-challenge experiments demonstrated that either vaccine induced protective immunity to homologous or heterologous RSSE or CEE virus challenge. The absence of antibody titer increases after challenge and the presence of antibodies to E and prM, but not NS1, both before and after challenge suggest that the vaccines prevented productive replication of the challenge virus. One vaccination with 0.5 microg of CEE virus DNA provided protective immunity for at least 2 months, and two vaccinations protected mice from challenge with CEE virus for at least 6 months.

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Selected References

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  1. Arikawa J., Schmaljohn A. L., Dalrymple J. M., Schmaljohn C. S. Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. J Gen Virol. 1989 Mar;70(Pt 3):615–624. doi: 10.1099/0022-1317-70-3-615. [DOI] [PubMed] [Google Scholar]
  2. Bos J. D. The skin as an organ of immunity. Clin Exp Immunol. 1997 Jan;107 (Suppl 1):3–5. [PubMed] [Google Scholar]
  3. Buckley A., Gould E. A. Neutralization of yellow fever virus studied using monoclonal and polyclonal antibodies. J Gen Virol. 1985 Dec;66(Pt 12):2523–2531. doi: 10.1099/0022-1317-66-12-2523. [DOI] [PubMed] [Google Scholar]
  4. Calisher C. H. Antigenic classification and taxonomy of flaviviruses (family Flaviviridae) emphasizing a universal system for the taxonomy of viruses causing tick-borne encephalitis. Acta Virol. 1988 Sep;32(5):469–478. [PubMed] [Google Scholar]
  5. Calisher C. H., Karabatsos N., Dalrymple J. M., Shope R. E., Porterfield J. S., Westaway E. G., Brandt W. E. Antigenic relationships between flaviviruses as determined by cross-neutralization tests with polyclonal antisera. J Gen Virol. 1989 Jan;70(Pt 1):37–43. doi: 10.1099/0022-1317-70-1-37. [DOI] [PubMed] [Google Scholar]
  6. Chu Y. K., Rossi C., Leduc J. W., Lee H. W., Schmaljohn C. S., Dalrymple J. M. Serological relationships among viruses in the Hantavirus genus, family Bunyaviridae. Virology. 1994 Jan;198(1):196–204. doi: 10.1006/viro.1994.1022. [DOI] [PubMed] [Google Scholar]
  7. Eisenbraun M. D., Fuller D. H., Haynes J. R. Examination of parameters affecting the elicitation of humoral immune responses by particle bombardment-mediated genetic immunization. DNA Cell Biol. 1993 Nov;12(9):791–797. doi: 10.1089/dna.1993.12.791. [DOI] [PubMed] [Google Scholar]
  8. Fuller D. H., Murphey-Corb M., Clements J., Barnett S., Haynes J. R. Induction of immunodeficiency virus-specific immune responses in rhesus monkeys following gene gun-mediated DNA vaccination. J Med Primatol. 1996 Jun;25(3):236–241. doi: 10.1111/j.1600-0684.1996.tb00021.x. [DOI] [PubMed] [Google Scholar]
  9. Fuller J. T., Fuller D. H., McCabe D., Haynes J. R., Widera G. Immune responses to hepatitis B virus surface and core antigens in mice, monkeys, and pigs after Accell particle-mediated DNA immunization. Ann N Y Acad Sci. 1995 Nov 27;772:282–284. doi: 10.1111/j.1749-6632.1995.tb44760.x. [DOI] [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. Gould E. A., Buckley A., Barrett A. D., Cammack N. Neutralizing (54K) and non-neutralizing (54K and 48K) monoclonal antibodies against structural and non-structural yellow fever virus proteins confer immunity in mice. J Gen Virol. 1986 Mar;67(Pt 3):591–595. doi: 10.1099/0022-1317-67-3-591. [DOI] [PubMed] [Google Scholar]
  12. Haynes J. R., Fuller D. H., Eisenbraun M. D., Ford M. J., Pertmer T. M. Accell particle-mediated DNA immunization elicits humoral, cytotoxic, and protective immune responses. AIDS Res Hum Retroviruses. 1994;10 (Suppl 2):S43–S45. [PubMed] [Google Scholar]
  13. Heinz F. X., Allison S. L., Stiasny K., Schalich J., Holzmann H., Mandl C. W., Kunz C. Recombinant and virion-derived soluble and particulate immunogens for vaccination against tick-borne encephalitis. Vaccine. 1995 Dec;13(17):1636–1642. doi: 10.1016/0264-410x(95)00133-l. [DOI] [PubMed] [Google Scholar]
  14. Heinz F. X., Berger R., Tuma W., Kunz C. A topological and functional model of epitopes on the structural glycoprotein of tick-borne encephalitis virus defined by monoclonal antibodies. Virology. 1983 Apr 30;126(2):525–537. doi: 10.1016/s0042-6822(83)80010-5. [DOI] [PubMed] [Google Scholar]
  15. Heinz F., Kunz C. Characterization of tick-borne encephalitis virus and immunogenicity of its surface components in mice. Acta Virol. 1977 Jul;21(4):308–316. [PubMed] [Google Scholar]
  16. Holzmann H., Stiasny K., Ecker M., Kunz C., Heinz F. X. Characterization of monoclonal antibody-escape mutants of tick-borne encephalitis virus with reduced neuroinvasiveness in mice. J Gen Virol. 1997 Jan;78(Pt 1):31–37. doi: 10.1099/0022-1317-78-1-31. [DOI] [PubMed] [Google Scholar]
  17. Holzmann H., Vorobyova M. S., Ladyzhenskaya I. P., Ferenczi E., Kundi M., Kunz C., Heinz F. X. Molecular epidemiology of tick-borne encephalitis virus: cross-protection between European and Far Eastern subtypes. Vaccine. 1992;10(5):345–349. doi: 10.1016/0264-410x(92)90376-u. [DOI] [PubMed] [Google Scholar]
  18. Iacono-Connors L. C., Smith J. F., Ksiazek T. G., Kelley C. L., Schmaljohn C. S. Characterization of Langat virus antigenic determinants defined by monoclonal antibodies to E, NS1 and preM and identification of a protective, non-neutralizing preM-specific monoclonal antibody. Virus Res. 1996 Aug;43(2):125–136. doi: 10.1016/0168-1702(96)01325-1. [DOI] [PubMed] [Google Scholar]
  19. Kaufman B. M., Summers P. L., Dubois D. R., Eckels K. H. Monoclonal antibodies against dengue 2 virus E-glycoprotein protect mice against lethal dengue infection. Am J Trop Med Hyg. 1987 Mar;36(2):427–434. doi: 10.4269/ajtmh.1987.36.427. [DOI] [PubMed] [Google Scholar]
  20. Kimura-Kuroda J., Yasui K. Protection of mice against Japanese encephalitis virus by passive administration with monoclonal antibodies. J Immunol. 1988 Nov 15;141(10):3606–3610. [PubMed] [Google Scholar]
  21. Konishi E., Mason P. W. Proper maturation of the Japanese encephalitis virus envelope glycoprotein requires cosynthesis with the premembrane protein. J Virol. 1993 Mar;67(3):1672–1675. doi: 10.1128/jvi.67.3.1672-1675.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Konishi E., Pincus S., Paoletti E., Laegreid W. W., Shope R. E., Mason P. W. A highly attenuated host range-restricted vaccinia virus strain, NYVAC, encoding the prM, E, and NS1 genes of Japanese encephalitis virus prevents JEV viremia in swine. Virology. 1992 Sep;190(1):454–458. doi: 10.1016/0042-6822(92)91233-k. [DOI] [PubMed] [Google Scholar]
  23. Konishi E., Pincus S., Paoletti E., Shope R. E., Burrage T., Mason P. W. Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection. Virology. 1992 Jun;188(2):714–720. doi: 10.1016/0042-6822(92)90526-u. [DOI] [PubMed] [Google Scholar]
  24. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kunz C., Heinz F. X., Hofmann H. Immunogenicity and reactogenicity of a highly purified vaccine against tick-borne encephalitis. J Med Virol. 1980;6(2):103–109. doi: 10.1002/jmv.1890060202. [DOI] [PubMed] [Google Scholar]
  26. Labuda M., Austyn J. M., Zuffova E., Kozuch O., Fuchsberger N., Lysy J., Nuttall P. A. Importance of localized skin infection in tick-borne encephalitis virus transmission. Virology. 1996 May 15;219(2):357–366. doi: 10.1006/viro.1996.0261. [DOI] [PubMed] [Google Scholar]
  27. Lu S., Arthos J., Montefiori D. C., Yasutomi Y., Manson K., Mustafa F., Johnson E., Santoro J. C., Wissink J., Mullins J. I. Simian immunodeficiency virus DNA vaccine trial in macaques. J Virol. 1996 Jun;70(6):3978–3991. doi: 10.1128/jvi.70.6.3978-3991.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mason P. W., Dalrymple J. M., Gentry M. K., McCown J. M., Hoke C. H., Burke D. S., Fournier M. J., Mason T. L. Molecular characterization of a neutralizing domain of the Japanese encephalitis virus structural glycoprotein. J Gen Virol. 1989 Aug;70(Pt 8):2037–2049. doi: 10.1099/0022-1317-70-8-2037. [DOI] [PubMed] [Google Scholar]
  29. Mason P. W., Pincus S., Fournier M. J., Mason T. L., Shope R. E., Paoletti E. Japanese encephalitis virus-vaccinia recombinants produce particulate forms of the structural membrane proteins and induce high levels of protection against lethal JEV infection. Virology. 1991 Jan;180(1):294–305. doi: 10.1016/0042-6822(91)90034-9. [DOI] [PubMed] [Google Scholar]
  30. Mathews J. H., Roehrig J. T. Elucidation of the topography and determination of the protective epitopes on the E glycoprotein of Saint Louis encephalitis virus by passive transfer with monoclonal antibodies. J Immunol. 1984 Mar;132(3):1533–1537. [PubMed] [Google Scholar]
  31. Meegan J. M., Yedloutschnig R. J., Peleg B. A., Shy J., Peters C. J., Walker J. S., Shope R. E. Enzyme-linked immunosorbent assay for detection of antibodies to Rift Valley fever virus in ovine and bovine sera. Am J Vet Res. 1987 Jul;48(7):1138–1141. [PubMed] [Google Scholar]
  32. Pertmer T. M., Eisenbraun M. D., McCabe D., Prayaga S. K., Fuller D. H., Haynes J. R. Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine. 1995;13(15):1427–1430. doi: 10.1016/0264-410x(95)00069-d. [DOI] [PubMed] [Google Scholar]
  33. Pincus S., Mason P. W., Konishi E., Fonseca B. A., Shope R. E., Rice C. M., Paoletti E. Recombinant vaccinia virus producing the prM and E proteins of yellow fever virus protects mice from lethal yellow fever encephalitis. Virology. 1992 Mar;187(1):290–297. doi: 10.1016/0042-6822(92)90317-i. [DOI] [PubMed] [Google Scholar]
  34. Rambukkana A., Bos J. D., Irik D., Menko W. J., Kapsenberg M. L., Das P. K. In situ behavior of human Langerhans cells in skin organ culture. Lab Invest. 1995 Oct;73(4):521–531. [PubMed] [Google Scholar]
  35. Schalich J., Allison S. L., Stiasny K., Mandl C. W., Kunz C., Heinz F. X. Recombinant subviral particles from tick-borne encephalitis virus are fusogenic and provide a model system for studying flavivirus envelope glycoprotein functions. J Virol. 1996 Jul;70(7):4549–4557. doi: 10.1128/jvi.70.7.4549-4557.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Stingl G. The skin: initiation and target site of immune responses. Recent Results Cancer Res. 1993;128:45–57. doi: 10.1007/978-3-642-84881-0_4. [DOI] [PubMed] [Google Scholar]
  37. Ulmer J. B., Deck R. R., Yawman A., Friedman A., Dewitt C., Martinez D., Montgomery D. L., Donnelly J. J., Liu M. A. DNA vaccines for bacteria and viruses. Adv Exp Med Biol. 1996;397:49–53. doi: 10.1007/978-1-4899-1382-1_7. [DOI] [PubMed] [Google Scholar]
  38. Ulmer J. B., Donnelly J. J., Deck R. R., DeWitt C. M., Liu M. A. Immunization against viral proteins with naked DNA. Ann N Y Acad Sci. 1995 Nov 27;772:117–125. doi: 10.1111/j.1749-6632.1995.tb44737.x. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Whalen R. G. DNA vaccines for emerging infectious diseases: what if? Emerg Infect Dis. 1996 Jul-Sep;2(3):168–175. doi: 10.3201/eid0203.960302. [DOI] [PMC free article] [PubMed] [Google Scholar]

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