Effect of IL-2 co-expressed or co-inoculated with immuno-dominant epitopes from VP1 protein of FMD virus on immune responses in BALB/c mice

Document Type: Original Article

Authors

1 Department of Animal Science, Ferdowsi University of Mashhad, Mashhad, Iran

2 Recombinant Proteins Research Group, Research Institute of Biotechnology and genetic group, Ferdowsi University of Mashhad, Mashhad, Iran

3 Department of Exercise Physiology, Faculty of Sport Science, University of Mazandaran, Babolsar, Iran 4 Razi Vaccine and Serum Research Institute, Mashhad, Iran

4 Razi Vaccine and Serum Research Institute, Mashhad, Iran

Abstract

Objective(s): The results of studies on vaccine development for foot-and-mouth disease (FMD) virus show that the use of inactivated vaccines for FMD virus is not completely effective. Novel vaccinations based on immuno-dominant epitopes have been shown to induce immune responses. Furthermore, for safety of immunization, access to efficient adjuvants against FMD virus seems to be critical.
Materials and Methods: In this study, we produced epitope recombinant vaccines from the VP1 protein of the FMD virus for serotype O of Iran. Constructs were included polytope (tandem-repeat multiple-epitope), polytope coupled with interleukin-2 (polytope-IL 2) as a molecular adjuvant and IL-2. Three expression vectors were constructed and expressed in Escherichia coli BL21 (DE3). To evaluate whether these recombinant vaccines induce immune responses, BALB/c mice were injected with the recombinant vaccines and their immune responses were compared with a negative control group. The humoral and cellular immune responses were measured by ELISA.
Results: The results showed that IL-2 co-expressed or co-inoculated with Polytope protein enhances the immune effect of multiple epitope recombinant vaccine against FMD virus. The results of total immunoglobulin G (IgG), IgG1, and IgG2a levels and secretion of interferon gamma (IFN-γ), IL-4 and IL-10 revealed that there were significant differences between negative control group and other injected mice with the recombinant vaccines (P<0.05).
Conclusion: Observations indicated that the epitope recombinant plasmid of the VP1 protein co-expressed or co-inoculated with IL-2 was effective in inducing an enhanced immune response. Therefore, IL-2 can be recommended as a potential adjuvant for epitope recombinant vaccine of the VP1 protein from FMD virus.

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1. Kim SA, Liang CM, Cheng IC, Cheng YC, Chiao MT, Tseng CJ, et al. DNA vaccination against foot-and-mouth disease via electroporation: study of molecular approaches for enhancing VP1 antigenicity. J Gene Med 2006;8:1182-1191.
2. Mason PW, Grubman MJ, Baxt B. Molecular basis of pathogenesis of FMDV. Virus Res 2003; 91: 9-32.
3. Kupper H, Keller W, Kurz C, Forss S, Schaller H, Franze R, et al. Cloning of cDNA of major antigen of foot-and-mouth disease virus and expression in E. coli. Nature 1981; 289: 555-559.
4. Saiz M, Nunez JI, Jimenez-Clavero MA, Baranowski E, Sobrino F. Foot-and-mouth disease virus: biology and prospects for disease control. Microbes Infect 2002; 4: 1183-1192.
5. Sutmoller P, Olascoaga RC. The risks posed by the importation of animals vaccinated against foot and mouth disease and products derived from vaccinated animals: a review. Rev Sci Tech 2003; 22: 823–835.
6. Barteling SJ, Vreeswijk J. Developments in foot-and-mouth disease vaccines. Vaccine 1991; 9: 75–88.
7. Doel TR. FMD vaccines. Virus Res 2003; 91:81–89.
8. Du Y, Dai J, Li Y, Li C, Qi J, Duan S, Jiang P. Immune responses of recombinant adenovirus co-expressing VP1 of foot-and-mouth disease virus and porcine interferon alpha in mice and guinea pigs, Veterinary. Immunol. Immunopathol 2008;124: 274-283.
9. Chinsangaram J, Mason PW, Grubman MJ. Protection of swine by live and inactivated vaccines prepared from a leader proteinase-deficient serotype A12 foot-and-mouth disease virus. Vaccine 1998; 16:1516-1622.
10. 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; 232: 639-641.
11. Liu XS, Wang YL, Zhang YG, Fang YZ, Pan L, Lu JL, et al. Identification of H-2d restricted T cell epitope of foot-and-mouth disease virus structural protein VP1. Virol J 2011; 7:426.
12. Fang M, Li J, Wang H, Yang M, Zhang Y, Zhou L, et al. Correlation between efficacy and structure of recombinant epitope vaccines against bovine type O foot and mouth disease virus. Biotechnol Lett 2012;34: 839-847.  
13. Morgan D, Moore D. Protection of cattle and swine against foot-and-mouth disease, using biosynthetic peptide vaccines. Am J Vet Res 1990;51: 40-45.
14. Zhang L, Zhang J, Chen HT, Zhou JH, Li NM, Ding YZ, et al. Research in advance for FMD Novel Vaccines.Virol J 2011; 8:268.
15. Zhang C, Wang B, Wang M. GM-CSF and IL-2 as adjuvant enhance the immune effect of protein vaccine against foot-and-mouth disease. Virol J 2011;8: 7.
16. Doosti M, Nassiri MR, Tahmoorespur M, Haghparast A, Zibaei S. Design and construction of multiple-epitope recombinant vaccine against foot-and-mouth disease virus type O. Research On Animal Production 2017; 8: 115-123.
17. Shao JJ, Wong C, Lin T, Lee SK, Cong GZ, Sin FW, et al. Promising multiple-epitope recombinant vaccine against foot-and-mouth disease virus type O in swine. Clin Vaccine Immunol 2011;18: 143-149.  
18. Bradford MM. A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal Biochem1976; 72:248-254. 19. Masoudi S, Mohammadi AA, Mahboudi F, Roustai, MH, Khedmati K. Molecular Cloning of VP1 gene of Foot-and-Mouth Disease Virus Type Ol/lran. Arch. Razi ln 2001; 51.
20. Qiumei S , Guisheng G , Yanying Z , Hua X , Zengqiang Y,  Hongxuan H. Cloning of structural protein VPI gene of foot and mouth disease virus and its expression in Escherichia coli.  J Animal Veterinary Adv 2012; 11:426-430.
21. Bae JY, Moon SH, Choi JA, Park JS, Hahn BS, Kim KY, et al. Recombinant DNA and protein vaccines for foot-and-mouth disease induce humoral and cellular immune responses in mice. Immune Netw 2009;9: 265-273.
22. Gao SD, Du JZ, Chang HY, Cong GZ, Shao JJ, Lin T, et al. B cell epitopes within VP1 of type O foot-and-mouth disease virus for detection of viral antibodies. Virol Sin 2010;25: 18-26.
23. Zhang Z, Hutching G, Kitching P, Alexandersen S. The effects of gamma interferon on replication of foot-and-mouth disease virus in persistently infected bovine cells. Arch Virol 2002;147:2157-2167.
24. Czajkowsky DM, Hu J, Shao Z, Pleass RJ. Fc-fusion proteins: new developments and future perspectives. EMBO Mol Med 2012; 4:1015-1028.
25. Shi XJ, Wang B, Zhang C, Wang M. Expressions of Bovine IFN-γ and Foot-and-Mouth Disease VP1 antigen in P. pastoris and their effects on mouse immune response to FMD antigens. Vaccine 2006;24: 82-89.
26. Yang CD, Liao JT, Lai CY, Jong MH, Liang CM, Lin YL, et al. Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes. BMC Biotechnol 2007; 7: 62.
27.  Du J, Chang H, Cong G, ShaoJ, Lin T, Shang Y, et al. Complete nucleotide sequence of a Chinese serotype Asia1 vaccine strain of foot-and-mouth disease virus. Virus Genes 2007; 35:635-642.
28. Gao F, Feng L, Zhang Q, Yan R, Li YG, Li XS. Immunogenicity of Two FMDV nonameric peptides encapsulated in liposomes in mice and the protective efficacy in guinea pigs. PLoS One 2013;8: e68658.
29. Park JH, Kim SJ, Oem JK, Lee KN, Kim YJ, Kye SJ, et al. Enhanced immune response with foot and mouth disease virus VP1 and interleukin-1 fusion genes. J Vet Sci 2006; 7: 257-262.