Influence of introduction of interleukin-2 and interleukin-12 into experimental marker DNA-vaccine

  • Ia. O. Pokholenko
  • T. P. Gulko
  • V. A. Kordium

Abstract

Aim. To determine the effects of the combined administration of recombinant expression vectors containing genes of murine interleukin-2 and interleukin-12 on humoral immune response, elicited by the experimental marker DNA-vaccine against classical swine fever. Methods. Expression of chimeric proteins in vitro and in vivo was determined by western-blot analysis. The antibodies specific to target antigens in blood serum have been detected by ELISA. Results. A series of recombinant plasmid vectors containing the genes of murine interleukin-2 and chimeric murine interleukin-12 have been developed. It has been shown that target chimeric proteins were expressed from the developed vectors both in vitro in HEK293 and in vivo in murine muscle tissue. The use of combined administration of murine interleukin-2 and interleukin-12 genes resulted in significant enhancement of titer of the anti-E2 and anti-β-galactosidase IgG, induced by vaccination with experimental marker DNA-vaccine against CSF, and model DNA-vaccine respectively. Conclusions. The data obtained show that the introduction of recombinant expressing vectors containing genes of murine interleukin-2 and interleukin-12 into vaccine preparations enhances humoral immune response elicited by the experimental marker DNA-vaccine against CSF and modelDNA-vaccine.

Keywords: DNA-vaccine, humoral immune response, interleukin-2, interleukin-12, classical swine fever.

References

Saade F., Petrovsky N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines. 2012. Vol. 11. P. 189–209. doi: 10.1586/erv.11.188 .

Kutzler M.A., Weiner D.B. DNA vaccines: ready for prime time? Nat. Rev. Genet. 2008. Vol. 9. P. 776–788. doi: 10.1038/nrg2432.

Pokholenko I.A., Ruban T.A., Sukhorada O.M., Deriabin O.M., Tytok T.G., Kordium V.A. The development of DNA-vaccine against classical swine fever. Biopolym. Cell. 2007. Vol. 23. P. 93–99. doi: http://dx.doi.org/10.7124/bc.00075A .

Collins R.A., Oldham G. Recombinant human interleukin 2 induces proliferation and immunoglobulin secretion by bovine

B-cells: tissue differences and preferential enhancement of immunoglobulin A. Vet. Immunol. Immunopathol. 1993. Vol. 36. P. 31–43. doi: https://doi.org/10.1016/0165-2427(93)90004-N.

Tovey M.G., Lallemand C. Adjuvant activity of cytokines. Methods Mol. Biol. 2010. Vol. 626. P. 287–309. doi: 10.1007/978-1-60761-585-9_19.

Chow Y.H., Chiang B.L., Lee Y.L., Chi W.K., Lin W.C., Chen Y.T., Tao M.H. Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J. Immunol. 1998. Vol. 160. P. 1320–1329.

Tian D.-Y., Sun Y., Wai S.F., Lee F.K., Meng Q.-L., Suen K.M., Wang N., Han W., Li S., Li Y.-F., Li D., Ling L.J., Liao Y.J., Qiu H.J. Enhancement of the immunogenicity of an alphavirus replicon-based DNA vaccine against classical swine fever by electroporation and coinjection with a plasmid expressing porcine interleukin 2. Vaccine. 2012. Vol. 30. P. 3587–3594. doi: 10.1016/j.vaccine.2012.03.049.

Jacobson J.M., Zheng L., Wilson C.C., Tebas P., Matining R.M., Egan M.A., Eldridge J., Landay A.L., Clifford D.B., Luetke-meyer A.F., Tiu J., Martinez A.L., Janik J., Spitz T.A., Hural J., McElrath J., Frahm N. ACTG A5281 Protocol Team. The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection. J. Acquir. Immune Defic. Syndr. 2016. Vol. 71. P. 163–171. doi: 10.1097/QAI.0000000000000830.

Gately M.K., Desai B.B., Wolitzky A.G., Quinn P.M., Dwyer C.M., Podlaski F.J., Familletti P.C., Sinigaglia F., Chizonnite R., Gubler U. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J. Immunol. 1991. Vol. 147. P. 874–882.

Jelinek D.F., Braaten J.K. Role of IL-12 in human B lymphocyte proliferation and differentiation. J. Immunol. 1995. Vol. 154 (4). P. 1606–1613.

Wienhold D., Armengol E., Marquardt A., Marquardt C., Voigt H., Büttner M., Saalmüller A., Pfaff E. Immunomodulatory effect of plasmids co-expressing cytokines in classical swine fever virus subunit gp55/E2-DNA vaccination. Vet. Res. 2005. Vol. 36. P. 571–587. doi: https://doi.org/10.1051/vetres:200501910.1051/vetres:2005019.

Schoenhaut D.S., Chua A.O., Wolitzky A.G., Quinn P.M., Dwyer C.M., McComas W., Familletti P.C., Gately M.K., Gubler U. Cloning and expression of murine IL-12. J. Immunol. 1992. Vol. 148. P. 3433–3440.

Tarradas J., Argilaguet J.M., Rosell R., Nofrarías M., Crisci E., Córdoba L., Pérez-Martín E., Díaz I., Rodríguez F., Domingo M. et al. Interferon-gamma induction correlates with protection by DNA vaccine expressing E2 glycoprotein against classical swine fever virus infection in domestic pigs. Vet. Microbiol. 2010. Vol. 142. P. 51–58. doi: 10.1016/j.vetmic.2009.09.043.

Kaufman H.L., Flanagan K., Lee C.S.D., Perretta D.J., Horig H. Insertion of interleukin-2 (IL-2) and interleukin-12 (IL-12) genes into vaccinia virus results in effective anti-tumor responses without toxicity. Vaccine. 2002. Vol. 20. P. 1862–1869. doi: https://doi.org/10.1016/S0264-410X(02)00032-4.

Pokholenko I.O., Titok T.G., Sukhorada O.M., Ruban T.A. Development of model DNA-vaccine. Biopolym. Cell. 2005. Vol. 21. P. 270–274. doi: http://dx.doi.org/10.7124/bc.0006F1.

Sambrook J., Fritsch E.F., Maniatis T. Molecular cloning: a laboratory manual, 2nd ed. Cold Spring Harbor (N.Y.): Cold Spring Harbor Laboratory Press. 1989. 625 p.