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Article Open Access

Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor

  • Authors:
    • Yongzhen Zhai
    • Yan Zhou
    • Ximei Li
    • Guohe Feng
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
    Copyright: © Zhai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 199-209
    |
    Published online on: March 4, 2015
       https://doi.org/10.3892/mmr.2015.3419
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Abstract

Plasmid‑encoded granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) is an adjuvant for genetic vaccines; however, how GM‑CSF enhances immunogenicity remains to be elucidated. In the present study, it was demonstrated that injection of a plasmid encoding the premembrane (prM) and envelope (E) protein of Japanese encephalitis virus and mouse GM‑CSF (pJME/GM‑CSF) into mouse muscle recruited large and multifocal conglomerates of macrophages and granulocytes, predominantly neutrophils. During the peak of the infiltration, an appreciable number of immature dendritic cells (DCs) appeared, although no T and B‑cells was detected. pJME/GM‑CSF increased the number of splenic DCs and the expression of major histocompatibility complex class II (MHCII) on splenic DC, and enhanced the antigenic capture, processing and presentation functions of splenic DCs, and the cell‑mediated immunity induced by the vaccine. These findings suggested that the immune‑enhancing effect by pJME/GM‑CSF was associated with infiltrate size and the appearance of integrin αx (CD11c)+cells. Chitosan‑pJME/GM‑CSF nanoparticles, prepared by coacervation via intramuscular injection, outperformed standard pJME/GM‑CSF administrations in DC recruitment, antigen processing and presentation, and vaccine enhancement. This revealed that muscular injection of chitosan‑pJME/GM‑CSF nanoparticles may enhance the immunoadjuvant properties of GM‑CSF.
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1 

Yamamoto A, Nakayama M, Kurosawa Y, et al: Development of a particle agglutination assay system for detecting Japanese encephalitis virus-specific human IgM, using hydroxyapatite-coated nylon beads. J Virol Methods. 104:195–201. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Solomon T and Vaughn DW: Pathogenesis and clinical features of Japanese encephalitis and West Nile virus infections. Curr Top Microbiol Immunol. 267:171–194. 2002.PubMed/NCBI

3 

Hoke CH, Nisalak A, Sangawhipa N, et al: Protection against Japanese encephalitis by inactivated vaccines. N Engl J Med. 319:608–614. 1988. View Article : Google Scholar : PubMed/NCBI

4 

Ueba N, Kimura T, Nakajima S, Kurimura T and Kitaura T: Field experiments on live attenuated Japanese encephalitis virus vaccine for swine. Biken J. 21:95–103. 1978.PubMed/NCBI

5 

Xin YY, Ming ZG, Peng GY, Jian A and Min LH: Safety of a live-attenuated Japanese encephalitis virus vaccine (SA14-14-2) for children. Am J Trop Med Hyg. 39:214–217. 1988.PubMed/NCBI

6 

Plesner AM and Ronne T: Allergic mucocutaneous reactions to Japanese encephalitis vaccine. Vaccine. 15:1239–1243. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Andersen MM and Rønne T: Side-effects with Japanese encephalitis vaccine. Lancet. 337:10441991. View Article : Google Scholar : PubMed/NCBI

8 

Ruff TA, Eisen D, Fuller A and Kass R: Adverse reactions to Japanese encephalitis vaccine. Lancet. 338:881–882. 1991. View Article : Google Scholar : PubMed/NCBI

9 

Sakaguchi M, Yoshida M, Kuroda W, Harayama O, Matsunaga Y and Inouye S: Systemic immediate-type reactions to gelatin included in Japanese encephalitis vaccines. Vaccine. 15:121–122. 1997. View Article : Google Scholar : PubMed/NCBI

10 

Liu MA: DNA vaccines: a review. J InternMed. 253:402–410. 2003.

11 

Putnak R, Porter K and Schmaljohn C: DNA vaccines for flavi-viruses. Adv Virus Res. 61:445–468. 2003.

12 

Konishi E, Yamaoka M, Khin-Sane-Win, Kurane I, Takada K and Mason PW: The anamnestic neutralizing antibody response is critical for protection of mice from challenge following vaccination with a plasmid encoding the Japanese encephalitis virus premembrane and envelope genes. J Virol. 73:5527–5534. 1999.PubMed/NCBI

13 

Konishi E, Ajiro N, Nukuzuma C, Mason PW and Kurane I: Comparison of protective efficacies of plasmid DNAs encoding Japanese encephalitis virus proteins that induce neutralizing antibody or cytotoxic T lymphocytes in mice. Vaccine. 21:3675–3683. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Wu CJ, Li TL, Huang HW, Tao MH and Chan YL: Development of an effective Japanese encephalitis virus-specific DNA vaccine. Microbes Infect. 8:2578–2586. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Kaur R, Sachdeva G and Vrati S: Plasmid DNA immunization against Japanese encephalitis virus: immunogenicity of membrane-anchored and secretory envelope protein. J Infect Dis. 185:1–12. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Bharati K, Appaiahgari MB and Vrati S: Effect of cytokine-encoding plasmid delivery on immune response to Japanese encephalitis virus DNA vaccine in mice. Microbiol Immunol. 49:349–353. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Kutzler MA and Weiner DB: Developing DNA vaccines that call to dendritic cells. J Clin Invest. 114:1241–1244. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Daro E, Pulendran B, Brasel K, et al: Polyethylene glycol-modified GM-CSF expands CD11b(high)CD11c(high) but not CD11b(low) CD11c(high) murine dendritic cells in vivo: a comparative analysis with Flt3 ligand. J Immunol. 165:49–58. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Daro E, Butz E, Smith J, Teepe M, Maliszewski CR and McKenna HJ: Comparison of the functional properties of murine dendritic cells generated in vivo with Flt3 ligand, GM-CSF and Flt3 ligand plus GM-SCF. Cytokine. 17:119–130. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Hanada K, Tsunoda R and Hamada H: GM-CSF-induced in vivo expansion of splenic dendritic cells and their strong costimulation activity. J Leukoc Biol. 60:181–190. 1996.PubMed/NCBI

21 

Mach N, Gillessen S, Wilson SB, Sheehan C, Mihm M and Dranoff G: Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res. 60:3239–3246. 2000.PubMed/NCBI

22 

Dranoff G, Jaffee E, Lazenby A, et al: Vaccination with irradiated tumor cells engineered to secrete murine granu-locyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA. 90:3539–3543. 1993. View Article : Google Scholar

23 

Chiodoni C, Paglia P, Stoppacciaro A, Rodolfo M, Parenza M and Colombo MP: Dendritic cells infiltrating tumors cotransduced with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand genes take up and present endogenous tumor-associated antigens, and prime naive mice for a cytotoxic T lymphocyte response. J Exp Med. 190:125–133. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Zaharoff DA, Rogers CJ, Hance KW, Schlom J and Greiner JW: Chitosan solution enhances the immunoadjuvant properties of GM-CSF. Vaccine. 25:8673–8686. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Pouton CW and Seymour LW: Key issues in non-viral gene delivery. Adv Drug Deliv Rev. 46:187–203. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Crystal RG: The gene as the drug. Nat Med. 1:15–17. 1995. View Article : Google Scholar : PubMed/NCBI

27 

Garnett MC: Gene-delivery systems using cationic polymers. Crit Rev Ther Drug Carrier Syst. 16:147–207. 1999. View Article : Google Scholar

28 

Read RC, Naylor SC, Potter CW, et al: Effective nasal influenza vaccine delivery using chitosan. Vaccine. 23:4367–4374. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Vila A, Sánchez A, Janes K, Behrens I, Kissel T, Vila Jato JL and Alonso MJ: Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm. 57:123–131. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Van der Lubben IM, Kersten G, Fretz MM, Beuvery C, Coos Verhoef J and Junginger HE: Chitosan microparticles for mucosal vaccination against diphtheria: oral and nasal efficacy studies in mice. Vaccine. 21:1400–1408. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Mao HQ, Roy K, Troung-Le VL, et al: Chitosan-DNA nanopar-ticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release. 70:399–421. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Haddad D, Ramprakash J, Sedegah M, et al: Plasmid vaccine expressing granulocyte-macrophage colony-stimulating factor attracts infiltrates including immature dendritic cells into injected muscles. J Immunol. 165:3772–3781. 2000. View Article : Google Scholar : PubMed/NCBI

33 

Zhai YZ, Zhou Y, Ma L and Feng GH: The dominant roles of ICAM-1-encoding gene in DNA vaccination against Japanese encephalitis virus are the activation of dendritic cells and enhancement of cellular immunity. Cell Immunol. 281:1–10. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Zhai YZ, Li XM, Zhou Y and Feng GH: Intramuscular immunization with a plasmid DNA vaccine encoding prM-E protein from Japanese encephalitis virus: Enhanced immunogenicity by co-administration of GM-CSF gene and genetic fusions of prM-E protein and GM-CSF. Intervirology. 52:152–163. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Gordon S, Teichmann E, Young K, Finnie K, Rades T and Hook S: In vitro and in vivo investigation of thermosensitive chitosan hydrogels containing silica nanoparticles for vaccine delivery. Eur J Pharm Sci. 41:360–368. 2010. View Article : Google Scholar : PubMed/NCBI

36 

McKay PF, Barouch DH, Santra S, et al: Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4+ and CD8+T lymphocyte responses. Eur J Immunol. 34:1011–1020. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Oka Y, Akbar SM, Horiike N, Joko K and Onji M: Mechanism and therapeutic potential of DNA-based immunization against the envelope proteins of hepatitis B virus in normal and transgenic mice. Immunology. 103:90–97. 2001. View Article : Google Scholar : PubMed/NCBI

38 

Cella M, Sallusto F and Lanzavecchia A: Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol. 9:10–16. 1997. View Article : Google Scholar : PubMed/NCBI

39 

Banchereau J and Steinman RM: Dendritic cells and the control of immunity. Nature. 392:245–252. 1998. View Article : Google Scholar : PubMed/NCBI

40 

Mellman I, Turley SJ and Steinman RM: Antigen processing for amateurs and professionals. Trends Cell Biol. 8:231–237. 1998. View Article : Google Scholar : PubMed/NCBI

41 

Steinman RM: Dendritic cells and the control of immunity: enhancing the efficiency of antigen presentation. Mt Sinai J Med. 68:160–166. 2001.PubMed/NCBI

42 

Seferian PG and Martinez ML: Imune stimulating activity of two new chitosan containing adjuvant formulations. Vaccine. 19:661–668. 2000. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhai Y, Zhou Y, Li X and Feng G: Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor. Mol Med Rep 12: 199-209, 2015.
APA
Zhai, Y., Zhou, Y., Li, X., & Feng, G. (2015). Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor. Molecular Medicine Reports, 12, 199-209. https://doi.org/10.3892/mmr.2015.3419
MLA
Zhai, Y., Zhou, Y., Li, X., Feng, G."Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor". Molecular Medicine Reports 12.1 (2015): 199-209.
Chicago
Zhai, Y., Zhou, Y., Li, X., Feng, G."Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor". Molecular Medicine Reports 12, no. 1 (2015): 199-209. https://doi.org/10.3892/mmr.2015.3419
Copy and paste a formatted citation
x
Spandidos Publications style
Zhai Y, Zhou Y, Li X and Feng G: Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor. Mol Med Rep 12: 199-209, 2015.
APA
Zhai, Y., Zhou, Y., Li, X., & Feng, G. (2015). Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor. Molecular Medicine Reports, 12, 199-209. https://doi.org/10.3892/mmr.2015.3419
MLA
Zhai, Y., Zhou, Y., Li, X., Feng, G."Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor". Molecular Medicine Reports 12.1 (2015): 199-209.
Chicago
Zhai, Y., Zhou, Y., Li, X., Feng, G."Immune‑enhancing effect of nano‑DNA vaccine encoding a gene of the prME protein of Japanese encephalitis virus and BALB/c mouse granulocyte‑macrophage colony‑stimulating factor". Molecular Medicine Reports 12, no. 1 (2015): 199-209. https://doi.org/10.3892/mmr.2015.3419
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