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. 2006 Dec 1;11(4):449–460. doi: 10.2478/s11658-006-0036-0

Schistosoma japonicum: The design and experimental evaluation of a multivalent DNA vaccine

Chunyan Li 1,3, Longjiang Yu 1,✉, Zhi Liu 1, Lu Zhu, Yuan Hu 2, Min Zhu 1, Xiaohua Zhu 2, Youen Shi 2, Sijin Meng 1,3
PMCID: PMC6472735  PMID: 16874456

Abstract

The aim of this study was to construct and evaluate the immunity efficacy of the DNA multivalent vaccine pVIVO2SjFABP-23. The vaccine was constructed and produced as follows. Forty BALB/c mice were divided into four groups designated pVIVO2, pVIVO2Sj23, pVIVO2SjFABP and pVIVO2SjFABP-23. Each mouse was immunized with 100 μg of the corresponding plasmid DNA by intramuscular injection. 28 days post-vaccination, the mice were challenged with S. japonicum cercariae, and the worm and egg burdens were determined 42 days post-challenge. Serum samples were collected from all the mice before and after vaccination and at the end of the experiment, and used for antibody detection. The IFN-γ and IL-4 levels were quantified in the supernatants of specifically stimulated spleen cells. The number of worms was reduced by 52%, 40% and 42% in mice respectively immunized with pVIVO2SjFABP-23, pVIVO2Sj23 or pVIVO2SjFABP. A respective 61%, 38% and 39% egg reduction was determined relative to those mice that only received the empty pVIVO2 plasmid. pVIVO2SjFABP-23 immunization increased IgG levels against SWAP and SEA. Increased IFN-γ levels were detected in the supernatant of specific stimulated spleen cells from mice immunized with the 3 different constructs. The multivalent DNA vaccine developed induced higher levels of protection than the two monovalent tested vaccines.

Key words: DNA vaccine, Schistosoma japonicum, Sj23, SjFABP, Protective efficacy

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Abbreviations used

FABP

fatty acid binding protein

SEA

soluble egg antigen

Sj

Schistosoma japonicum

SOE

splicing by overlapping extension

SWAP

soluble adult worm antigens

WHO

world health organization

23

23 kDa membrane protein

References

  • 1.Ross A.G. Schistosomiasis. N. Engl. J. Med. 2002;346:1212–1220. doi: 10.1056/NEJMra012396. [DOI] [PubMed] [Google Scholar]
  • 2.Chitsulo L., Engels D., Montresor A., Savioli L. The global status of schistosomiasis and its control. Acta Trop. 2000;77:41–51. doi: 10.1016/s0001-706x(00)00122-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.WHO Expert Committee. WHO Technical Report Series. Geneva, Switzerland: World Health Organization; 2002. Prevention and control of schistosomiasis and soil-transmitted helminthiasis: report of the WHO expert committee; pp. 1–57. [PubMed] [Google Scholar]
  • 4.Van der Werf M.J., De Vlas S.J. Quantification of clinical morbidity associated with Schistosoma infection in sub-Saharan Africa. Acta Trop. 2003;86:125–139. doi: 10.1016/s0001-706x(03)00029-9. [DOI] [PubMed] [Google Scholar]
  • 5.Tan H.Z., Yang M.X., Wu Z.G., Zhou J., Liu A.Z., Li S.Q., Yang T.B., Zhou Y.B., Sun Z.Q. Rapid screening method for Schistosoma japonicum infection using questionnaires in flood area of the People’s Republic of China. Acta Trop. 2004;90:1–9. doi: 10.1016/j.actatropica.2003.09.008. [DOI] [PubMed] [Google Scholar]
  • 6.Gurunathan S., Klinman D., Seder R. DNA vaccines immunology, application and optimization. Annu Rev. Immunol. 2000;18:927–974. doi: 10.1146/annurev.immunol.18.1.927. [DOI] [PubMed] [Google Scholar]
  • 7.Alarcon J., Waine G., McManus D.P. DNA vaccines: technology and application as anti-parasite and antimicrobial agents. Adv. Parasitol. 1999;42:343–410. doi: 10.1016/s0065-308x(08)60152-9. [DOI] [PubMed] [Google Scholar]
  • 8.Kofta W., Wedrychowicz H. c-DNA vaccination against parasitic infections. advantages and disadvantages. Vet. Parasitol. 2001;100:3–12. doi: 10.1016/s0304-4017(01)00478-2. [DOI] [PubMed] [Google Scholar]
  • 9.Rosas G., Fragoso G., Garate T., Hernandez B., Ferrero P., Foster-Cuevas M., Parkhouse R.M., Harrison L.J., Briones S.L., Gonzalez L.M., Sciutto E. Protective immunity against Taenia crassiceps murine cysticercosis induced by DNA vaccination with a Taenia saginata tegument antigen. Microbes Infect. 2002;4:1417–1426. doi: 10.1016/s1286-4579(02)00025-4. [DOI] [PubMed] [Google Scholar]
  • 10.Wang Q.M., Sun S.H., Hu Z.L., Wu D., Wang Z.C. Immune response and protection elicited by DNA immunization against Taenia cysticercosis. Vaccine. 2003;21:1672–1680. doi: 10.1016/s0264-410x(02)00661-8. [DOI] [PubMed] [Google Scholar]
  • 11.Waine G., Alarcon J., McManus D.P. Genetic immunization of mice with DNA encoding the 23 kDa transmembrane surface protein of Schistosoma japonicum (Sj23) induces antigen-specific immunoglobulin G antibodies. Parasite Immunol. 1999;21:377–381. doi: 10.1046/j.1365-3024.1999.00221.x. [DOI] [PubMed] [Google Scholar]
  • 12.Siddiqui A.A., Phillips T., Charest H., Podesta R.B., Quinlin M.L., Pinkston J.K., Lloyd J.D., Pompa J., Villalovos R.M., Paz M. Enhancement of Sm-p80 (large subunit of calpain) induced protective immunity against Schistosoma mansoni through co-delivery of interleukin-2 and interleukin-12 in a DNA vaccine formulation. Vaccine. 2003;21:2882–2889. doi: 10.1016/s0264-410x(03)00159-2. [DOI] [PubMed] [Google Scholar]
  • 13.Zhang Y., Taylor M., Johansen M., Bickle Q. Vaccination of mice with a cocktail DNA vaccine induces a Th1-type immune response and partial protection against Schistosoma japonicum infection. Vaccine. 2002;20:724–730. doi: 10.1016/s0264-410x(01)00420-0. [DOI] [PubMed] [Google Scholar]
  • 14.Zhao W., Su C., Wu H.W., Hu X.M., Shen L., Ji M.L., Wang R.Z., Ma L., Chen S.Z., Zhang Z.S. Studies on immunoprotection in mice after immunization with Schistosoma japonicum fatty acid binding protein (SjFABPc) recombinant protein. Chinese Journal of Zoonoses. 2002;18:42–44. [PubMed] [Google Scholar]
  • 15.Li L.Z., Shi Y.E., Jiang K., Ning C.X., Deng W.W. Study on the immune effect of multianti genic DNA vaccine pBK-Sj26(Sj32)-Sj23 of Schistosoma japonicum. Acta Univ. Med. Tongji. 2001;30:404–406. [Google Scholar]
  • 16.Liu S.X., Song G.C., Xu Y. X., McManus D.P., Hotez P.J. Progress in the development of a vaccine against Schistosomiasis in China. Int. J. Infect. Dis. 1998;2:176–180. doi: 10.1016/s1201-9712(98)90124-2. [DOI] [PubMed] [Google Scholar]
  • 17.Zhou S.H., Liu S.X., Song G.C., Xu Y. X., Sun W. Protective immunity induced by the full-length cDNA encoding paramyosin of Chinese Schistosoma japonicum. Vaccine. 2000;18:3196–3204. doi: 10.1016/s0264-410x(99)00555-1. [DOI] [PubMed] [Google Scholar]
  • 18.Zhu Y.C., Ren J.G., Da’dara A., Harn D.A., Xu M., Si J., Yu C.X., Liang Y.S., Ye P., Yin X.R., He W., Xu Y.L., Gao Q., Hua W.Q. The protective effect of a Schistosoma japonicum Chinese strain 23kDa plasmid DNA vaccine in pigs is enhanced with IL-12. Vaccine. 2004;23:78–83. doi: 10.1016/j.vaccine.2004.04.031. [DOI] [PubMed] [Google Scholar]
  • 19.Gan Y., Shi Y.E., Bu L.Y., Zhu X.H., Ning C.X., Zhu H.G. Immune responses against Schistosoma japonicum after vaccinating mice with a multivalent DNA vaccine encoding integrated membrane protein Sj23 and cytokine interleukin-12. Chin. Med. J. 2004;117:1842–1846. [PubMed] [Google Scholar]
  • 20.Li L.Z., Shi Y.E. The protection of Sj23 DNA vaccine on mice. Chin. J. Schisto. Control. 1999;11:71–74. [Google Scholar]
  • 21.Zhu X.H., Shi Y.E. The Immunoprotective Effect of Co-inoculation of Schistosoma japonicum Fatty Acid Binding Protein (Sj14FABP) DNA and IL-12 in the Mouse. Herald of Medicine. 2005;24:268–270. [Google Scholar]
  • 22.Zhu X.H., Shi Y.E., Hu P., Ning C.X., Zhu H.G. Protective immunity induced by plasmid DNA encoding fatty acid binding protein of Schistosoma japonicum in mice. Chin. J. Schisto. Control. 2005;17:4–8. [Google Scholar]
  • 23.Yu C.X., Zhu Y.C., Yin X.R., Ren J.G., Si J., Xu Y.L., Shen L.N., He W. Protective immunity induced by the nucleic acid vaccine of fatty acid binding protein of Schistosoma japonicum Chinese strain (SjCFABP) in BALB/c mice. Chin. J. Schisto. Control. 2002;14:163–167. [Google Scholar]
  • 24.Jankovic D., Wynn T.A., Kullberg M.C., Hieny S., Caspar P., James S., Cheever A.W., Sher A. Optimal vaccination against Schistosoma mansoni requires the induction of both B cell-and IFN-gamma-dependent effect mechanisms. J. Immunol. 1999;162:345–351. [PubMed] [Google Scholar]
  • 25.Wynm T.A., Hoffmanm K.F. Defining a schistosomiasis vaccination strategy-is it really Th1 versus Th2? Parasitol. Today. 2000;16:497–501. doi: 10.1016/s0169-4758(00)01788-9. [DOI] [PubMed] [Google Scholar]
  • 26.Becker M.M., Kalinna B.H., Waine G.J., McManus D.P. Gene cloning, overproduction and purification of a functionally active cytoplasmic fatty acid-binding protein (SjFABPc) from the human blood fluke Schistosoma japonicum. Gene. 1994;148:321–325. doi: 10.1016/0378-1119(94)90706-4. [DOI] [PubMed] [Google Scholar]
  • 27.Gobert G.N., Stenzel D.J., Jones M.K., McManus D.P. Immunolocalization of the fatty acid-binding protein Sj FABPc within adult Schistosoma japonicum. Parasitology. 1997;115:33–39. doi: 10.1017/s0031182097008925. [DOI] [PubMed] [Google Scholar]
  • 28.Wright M.D., Melder A.M., Davern K.M., Mitchell G.F. Serologic activities of the 23 kDa integral membrane proteins of schistosomes. J. Immunol. 1991;147:4338–4342. [PubMed] [Google Scholar]
  • 29.Davern K.M., Wright M.D., Herrmann V.R., Mitchell G.F. Further characterisation of the Schistosoma japon-icum protein Sj26, a target antigen of an immunodiagnostic monoclonal antibody. Mol. Biochem. Parasitol. 1991;48:67–75. doi: 10.1016/0166-6851(91)90165-3. [DOI] [PubMed] [Google Scholar]
  • 30.Wu Z.D., Lu Z.Y., Yu X.B. Development of a vaccine against Schistosoma japonicum in China: a review. Acta Tropica. 2005;96:106–116. doi: 10.1016/j.actatropica.2005.08.005. [DOI] [PubMed] [Google Scholar]
  • 31.Ren J.G., Zhu Y.C., Harn D.A., Yu C.X., Yin X.R., Si J., He W., Xu M., Hua W.Q., Xu Y.L. Protective immunity induced with 23kDa membrane protein DNA vaccine of Schistosoma japonicum Chinese strain in infected C57BL/6 mice. Chin. J. Parasitol. Parasit. Dis. 2001;19:336–339. [PubMed] [Google Scholar]
  • 32.Waine G.J., Alarcon J.B., Qiu C., McManus D.P. Genetic immunization of mice with DNA encoding the 23 kDa transmembrane surface protein of Schistosoma japonicum (Sj23) induces antigen-specific immunoglobulin G antibodies. Parasite Immunol. 1999;21:377–381. doi: 10.1046/j.1365-3024.1999.00221.x. [DOI] [PubMed] [Google Scholar]
  • 33.Verity C., McManus D.P., Brindley P.J. Cellular responses to Schistosoma japonicum cathepsin D aartic protease. Parasite Immunol. 2002;24:363–367. doi: 10.1046/j.1365-3024.2002.00475.x. [DOI] [PubMed] [Google Scholar]
  • 34.McManus D.P., Bartley P.B. A vaccine against Asian schistosomiasis. Parasitol. Int. 2004;53:163–173. doi: 10.1016/j.parint.2004.01.006. [DOI] [PubMed] [Google Scholar]
  • 35.Demeure C.E., Rihet P., Abel L., Quattara M., Bourgoirs A., Dassein A.J. Resistance to S. mansoni in humans: influence of IgE/IgG4 in immunity to reinfection after chemotherapy. J. Infect. Dis. 1993;168:1000–1008. doi: 10.1093/infdis/168.4.1000. [DOI] [PubMed] [Google Scholar]
  • 36.Grzych J.M., De Bont J., Liu J., Neyrinck J.L., Fontaine J., Vercruysse J., Capron A. Relationship of impairment of schistosome 28-kilodalton glutathione S-transferase (GST) activity to express of immunity to Schistosoma mattheei in calves vaccinated with recombinant Schistosoma bovis 28-kilodalton GST. Infect. Immun. 1998;66:1142–1148. doi: 10.1128/iai.66.3.1142-1148.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]

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