Skip to main content

Advertisement

SpringerLink
Log in

Pharmacokinetics and risk evaluation of DNA vaccine against Schistosoma japonicum

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

DNA plasmid immunization is a novel approach of preventive and therapeutic vaccine. More than 100 DNA vaccines have been on preclinical or clinical phase trials, and four kinds of DNA vaccines for livestock have been approved by USDA, CFIA, and APVMA. Schistosomiasis is a worldwide parasitic disease, and vaccine immunization is supposed to be a promising approach to control the health crisis. On the basis of former preclinical studies, we further focused on the pharmacokinetics and risk evaluation of DNA vaccine in vivo. In the present study, enhanced green fluorescent protein (EGFP) report gene was fused with Schistosoma japonicum 23 kDa transmembrane protein antigen gene (Sj23) and constructed into DNA vaccine pVIVO2-Sj23.EGFP. After intramuscularly injecting 100 μg of purified DNA vaccine plasmid to immunizate BALB/c mice, we studied the tissue distribution of DNA plasmid and expressed Sj23.EGFP antigen, the persistence time of elicited antibodies, and the risk of DNA vaccine transferred into intestinal microorganisms. The results showed that DNA vaccine plasmid could be distributed into all tissues of the body after injection; however, only few organs including the injected muscle were detected DNA vaccine at postimmunization until the 100 days by PCR technology; the detection of green fluorescence protein displayed that DNA vaccine could be expressed in almost every tissue and organs; the ELISA assay indicated the immune antibody against Sj23 could persist over 70 days; and the DNA vaccine transferring intestinal flora results was negative. The results indicated that the DNA vaccine has systemic protection and long-lasting effectivity and is safe to intestinal flora.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Barry ME, Orson FM, Petry GR et al (1999) Role of endogenous endonucleases and tissue site in transfection and CpG-mediated immune activation after naked DNA injection. Hum Gene Ther 10:2461–2480

    Article  PubMed  CAS  Google Scholar 

  • Colley DG, Bergquist NR (1998) Schistosomiasis vaccines: research to development. Parasitol Today 14:99–104

    Article  PubMed  Google Scholar 

  • Yeh E, Gustafson K, Boulianne GL (1995) Green fluorescent protein as a vital marker and reporter of gene expression in Drosophila. Proc Natl Acad Sci USA 92:7036–7040

    Article  PubMed  CAS  Google Scholar 

  • FDA (2007) Considerations for plasmid DNA vaccines for infectious disease indications. Biotechnol Law Rep 6:641–642

    Google Scholar 

  • Frelin L, Brass A, Chen M et al (2010) Electroporation: a promising method for the nonviral delivery of DNA vaccines in humans? Drug News Perspect 23:647–653

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro-dos-Santos G, Verjovski-Almeida S, Leite LCC (2006) Schistosomiasis—a century searching for chemotherapeutic drugs. Parasitol Res 99:505–521

    Article  PubMed  Google Scholar 

  • Gao X, Kim KS, Liu D (2007) Nonviral gene delivery: what we know and what is next. AAPS J 9:92–104

    Article  Google Scholar 

  • Ahmad G, Zhang W, Torben W, Haskins C, Diggs S, Noor Z, Le L, Siddiqui AA (2009) Prime-boost and recombinant protein vaccination strategies using Sm-p80 protects against Schistosoma mansoni infection in the mouse model to levels previously attainable only by the irradiated cercarial vaccine. Parasitol Res 105:1767–1777

    Article  PubMed  Google Scholar 

  • Hanke T, McMichael AJ, Dennis MJ et al (2005) Biodistribution and persistence of an MVA-vectored candidate HIV vaccine in SIV-infected rhesus macaques and SCID mice. Vaccine 23:1507–1514

    Article  PubMed  CAS  Google Scholar 

  • Hohlweg U, Doerfler W (2001) On the fate of plant or other foreign genes upon the uptake in food or after intramuscular injection in mice. Mol Genet Genomics 265:225–233

    Article  PubMed  CAS  Google Scholar 

  • Horton RM, Hunt HD, Ho SN et al (1989) Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 77:61–68

    Article  PubMed  CAS  Google Scholar 

  • Kurath G, Garver KA, Corbeil S et al (2006) Protective immunity and lack of histopathological damage two years after DNA vaccination against infectious hematopoietic necrosis virus in trout. Vaccine 24:345–354

    Article  PubMed  CAS  Google Scholar 

  • Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788

    Article  PubMed  CAS  Google Scholar 

  • Langemann T, Koller VJ, Muhammad A et al (2010) The bacterial ghost platform system: production and applications. Bioeng Bugs 1:326–336

    Article  PubMed  Google Scholar 

  • Lew D, Parker SE, Latimer T et al (1995) Cancer gene therapy using plasmid DNA: pharmacokinetic study of DNA following injection in mice. Hum Gene Ther 6:553–564

    Article  PubMed  CAS  Google Scholar 

  • Li C, Liu Z, Zhu L et al (2006) Schistosoma japonicum: the design and experimental evaluation of a multivalent DNA vaccine. Cell Mol Biol Lett 11:449–460

    Article  PubMed  CAS  Google Scholar 

  • Loots K, Vleuqels B, Ons E et al (2006) Evaluation of the persistence and gene expression of an anti-Chlamydophila psittaci DNA vaccine in turkey muscle. BMC Vet Res 2:18

    Article  PubMed  Google Scholar 

  • Martin T, Parker SE, Hedstrom R et al (1999) Plasmid DNA malaria vaccine: the potential for genomic integration after intramuscular injection. Hum Gene Ther 20:759–768

    Article  Google Scholar 

  • Osaka G, Carey K, Cuthbertson A et al (1996) Pharmacokinetics, tissue distribution, and expression efficiency of plasmid [33P]DNA following intravenous administration of DNA/cationic lipid complexes in mice: use of a novel radionuclide approach. J Pharm Sci 85:612–618

    Article  PubMed  CAS  Google Scholar 

  • World Health Organization, WHO (2010) Schistosomiasis live report. (http://www.who.int/mediacentre/factsheets/fs115/en/index.html)

  • Parker SE, Borellini F, Wenk ML et al (1999) Plasmid DNA malaria vaccine: tissue distribution and safety studies in mice and rabbits. Hum Gene Ther 20:741–758

    Article  Google Scholar 

  • Pokorna D, Rubio I, Muller M (2008) DNA-vaccination via tattooing induces stronger humoral and cellular immune responses than intramuscular delivery supported by molecular adjuvants. Genet Vaccines Ther 6:4

    Article  PubMed  Google Scholar 

  • Pontes DS, Chatel JM, Langella P et al (2011) Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Protein Expr Purif 79:165–175

    Article  PubMed  CAS  Google Scholar 

  • Rochard A, Scherman D, Bigey P (2011) Genetic immunization with plasmid DNA mediated by electrotransfer. Hum Gene Ther 22:789–798

    Article  PubMed  CAS  Google Scholar 

  • Tsien RY (1998) The green fluorescent protein. Annu Rev Biochem 67:509–544

    Article  PubMed  CAS  Google Scholar 

  • Siddiqui AA, Ahmad G et al (2008) Experimental vaccines in animal models for schistosomiasis. Parasitol Res 102:825–833

    Article  PubMed  Google Scholar 

  • Siddiqui AA, Siddiqui BA, Ganley-Leal L (2011) Schistosomiasis vaccines. Hum Vaccine 7:1192–1197

    Article  CAS  Google Scholar 

  • Soliman MF, Ibrahim MM (2005) Antischistosomal action of atorvastatin alone and concurrently with medroxyprogesterone acetate on Schistosoma haematobium harboured in hamster: surface ultrastructure and parasitological study. Acta Trop 93:1–9

    Article  PubMed  CAS  Google Scholar 

  • Netherwood T, Gockling S, Graham J et al (2004) Assessing the survival of transgenic planic plant DNA in the human gastrointestinal tract. Nat Biotechnol 22:204–209

    Article  PubMed  CAS  Google Scholar 

  • Vilalta A, Mahajan RK, Hartikka J et al (2005) Poloxamer-formulated plasmid DNA-based human cytomegalovirus vaccine: evaluation of plasmid DNA biodistribution/persistence and integration. Hum Gene Ther 16:1143–1150

    Article  PubMed  CAS  Google Scholar 

  • Wolff JA, Malone RW et al (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  PubMed  CAS  Google Scholar 

  • Wei Q, Ye L, Xu J et al (2001) Tissue distribution and safety studies of DNA vaccine in mice. Chin J Zoonoses 5:9–11

    Google Scholar 

  • Wells DJ (2004) Gene therapy progress and prospects: electroporation and other physical methods. Gene Ther 11:1363–1369

    Article  PubMed  CAS  Google Scholar 

  • Hu Y, Shi Y-E, Yu L-J et al (2007) Studies on the protective immunity of Schistosoma japonicum bivalent DNA vaccine encoding Sj23 and Sj14. Exp Parasitol 115:379–386

    Article  CAS  Google Scholar 

  • Zhu L, Liu HF, Yu LJ et al (2010) Construction and immuno-protection evaluation of trivalent-epitope DNA Vaccine pVIVO2-SjFABP/Sj26. SjGAPDH. Chin Biotechnol 5:36–42

    Google Scholar 

  • Zhu L, Liu HF, Yu LJ et al (2011) Construction, purification, and evaluation of multivalent DNA vaccine against Schistosoma japonicum. Parasitol Res 108:115–121

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Ph.D. Programs Foundation of Ministry of Education of China (no. 20070487059), the Program for New Century Excellent Talents in University (NCET-06-0646), New Century High-level Talents of Hubei Province (20030929), and the National High Technology Research and Development Program of China (no. 2004AA2Z3212).

Author information

Authors and Affiliations

  1. College of Life Science and Technology, Huazhong University of Science and Technology, 430074, Wuhan, China

    Hai-Feng Liu, Wei Li, Ming-Bo Lu & Long-Jiang Yu

Authors
  1. Hai-Feng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ming-Bo Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Long-Jiang Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Long-Jiang Yu.

Additional information

Wei Li and Hai-Feng Liu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, HF., Li, W., Lu, MB. et al. Pharmacokinetics and risk evaluation of DNA vaccine against Schistosoma japonicum . Parasitol Res 112, 59–67 (2013). https://doi.org/10.1007/s00436-012-3104-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-012-3104-6

Keywords

Search

Navigation