Parasitology Research

, 105:1767

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

  • Gul Ahmad
  • Weidong Zhang
  • Workineh Torben
  • Chad Haskins
  • Sue Diggs
  • Zahid Noor
  • Loc Le
  • Afzal A. Siddiqui
Rapid Communication

Abstract

Advent of an effective schistosome vaccine would contribute significantly toward reducing the disease spectrum and transmission of schistosomiasis. We have targeted a functionally important antigen, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective and antifecundity potentials, and important role in the immune evasion process. In this study, we report that using two vaccination approaches (prime boost and recombinant protein), Sm-p80-based vaccine formulation(s) confer up to 70% reduction in worm burden in mice. Animals immunized with the vaccine exhibited a decrease in egg production by up to 75%. The vaccine elicited strong immune responses that included IgM, IgA, and IgG (IgG1, IgG2a, IgG2b, and IgG3) in vaccinated animals. Splenocytes proliferated in response to Sm-p80 produced Th1 and Th17 response enhancing cytokines. These results again emphasize the potential of Sm-p80 as a viable vaccine candidate for schistosomiasis.

References

  1. Ahmad G, Torben W, Zhang W, Wyatt M, Siddiqui AA (2009a) Sm-p80-based DNA vaccine formulation induces potent protective immunity against Schistosoma mansoni. Parasite Immunol 31:156–161CrossRefPubMedGoogle Scholar
  2. Ahmad G, Zhang W, Torben W, Damian RT, Wolf RF, White GL, Chavez-Suarez M, Kennedy RC, Siddiqui AA (2009b) Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model. Vaccine 27:2830–2837CrossRefPubMedGoogle Scholar
  3. Bergquist NR, Leonardo LR, Mitchell GF (2005) Vaccine-linked chemotherapy: can schistosomiasis control benefit from an integrated approach? Trends Parasitol 21:112–117CrossRefPubMedGoogle Scholar
  4. Bergquist R, Utzinger J, McManus DP (2008) Trick or treat: the role of vaccines in integrated schistosomiasis control. PLoS Negl Trop Dis 2:e244CrossRefPubMedGoogle Scholar
  5. Bettelli E, Korn T, Oukka M, Kuchroo VK (2008) Induction and effector functions of T(H)17 cells. Nature 453:1051–1057CrossRefPubMedGoogle Scholar
  6. Brandt K, Bulfone-Paus S, Foster DC, Ruckert R (2003) Interleukin-21 inhibits dendritic cell activation and maturation. Blood 102:4090–4098CrossRefPubMedGoogle Scholar
  7. Da’dara AA, Harn DA (2005) DNA vaccines against tropical parasitic diseases. Expert Rev Vaccines 4:575–589CrossRefPubMedGoogle Scholar
  8. Da’dara AA, Lautsch N, Dudek T, Novitsky V, Lee TH, Essex M, Harn DA (2006) Helminth infection suppresses T-cell immune response to HIV-DNA-based vaccine in mice. Vaccine 24:5211–5219CrossRefPubMedGoogle Scholar
  9. El-Khoby T, Galal N, Fenwick A, Barakat R, El-Hawey A, Nooman Z, Habib M, bdel-Wahab F, Gabr NS, Hammam HM, Hussein MH, Mikhail NN, Cline BL, Strickland GT (2000) The epidemiology of schistosomiasis in Egypt: summary findings in nine governorates. Am J Trop Med Hyg 62:88–99PubMedGoogle Scholar
  10. Ganley-Leal LM, Guarner J, Todd CW, ‘Dara AA, Freeman GL Jr, Boyer AE, Harn DA, Secor WE (2005) Comparison of Schistosoma mansoni irradiated cercariae and Sm23 DNA vaccines. Parasite Immunol 27:341–349CrossRefPubMedGoogle Scholar
  11. Godinez I, Haneda T, Raffatellu M, George MD, Paixao TA, Rolan HG, Santos RL, Dandekar S, Tsolis RM, Baumler AJ (2008) T cells help to amplify inflammatory responses induced by Salmonella enterica serotype Typhimurium in the intestinal mucosa. Infect Immun 76:2008–2017CrossRefPubMedGoogle Scholar
  12. Hagan P, Sharaf O (2003) Schistosomiasis vaccines. Expert Opin Biol Ther 3:1271–1278CrossRefPubMedGoogle Scholar
  13. Hewitson JP, Hamblin PA, Mountford AP (2005) Immunity induced by the radiation-attenuated schistosome vaccine. Parasite Immunol 27:271–280CrossRefPubMedGoogle Scholar
  14. Hota-Mitchell S, Siddiqui AA, Dekaban GA, Smith J, Tognon C, Podesta RB (1997) Protection against Schistosoma mansoni infection with a recombinant baculovirus-expressed subunit of calpain. Vaccine 15:1631–1640CrossRefPubMedGoogle Scholar
  15. Hota-Mitchell S, Clarke MW, Podesta RB, Dekaban GA (1999) Recombinant vaccinia viruses and gene gun vectors expressing the large subunit of Schistosoma mansoni calpain used in a murine immunization-challenge model. Vaccine 17:1338–1354CrossRefPubMedGoogle Scholar
  16. Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, Savioli L (2007) Control of neglected tropical diseases. N Engl J Med 357:1018–1027CrossRefPubMedGoogle Scholar
  17. Jankovic D, Aslund L, Oswald IP, Caspar P, Champion C, Pearce E, Coligan JE, Strand M, Sher A, James SL (1996) Calpain is the target antigen of a Th1 clone that transfers protective immunity against Schistosoma mansoni. J Immunol 157:806–814PubMedGoogle Scholar
  18. Jankovic D, Wynn TA, Kullberg MC, Hieny S, Caspar P, James S, Cheever AW, Sher A (1999) Optimal vaccination against Schistosoma mansoni requires the induction of both B cell- and IFN-gamma-dependent effector mechanisms. J Immunol 162:345–351PubMedGoogle Scholar
  19. Kishimoto C, Kawamata H, Sakai S, Shinohara H, Ochiai H (2001) Enhanced production of macrophage inflammatory protein 2 (MIP-2) by in vitro and in vivo infections with encephalomyocarditis virus and modulation of myocarditis with an antibody against MIP-2. J Virol 75:1294–1300CrossRefPubMedGoogle Scholar
  20. Lauwerys BR, Garot N, Renauld JC, Houssiau FA (2000) Cytokine production and killer activity of NK/T-NK cells derived with IL-2, IL-15, or the combination of IL-12 and IL-18. J Immunol 165:1847–1853PubMedGoogle Scholar
  21. Lebens M, Sun JB, Czerkinsky C, Holmgren J (2004) Current status and future prospects for a vaccine against schistosomiasis. Expert Rev Vaccines 3:315–328CrossRefPubMedGoogle Scholar
  22. McManus DP, Loukas A (2008) Current status of vaccines for schistosomiasis. Clin Microbiol Rev 21:225–242CrossRefPubMedGoogle Scholar
  23. Minard P, Dean DA, Jacobson RH, Vannier WE, Murrell KD (1978) Immunization of mice with cobalt-60 irradiated Schistosoma mansoni cercariae. Am J Trop Med Hyg 27:76–86PubMedGoogle Scholar
  24. Montgomery RA, Dallman MJ (1991) Analysis of cytokine gene expression during fetal thymic ontogeny using the polymerase chain reaction. J Immunol 147:554–560PubMedGoogle Scholar
  25. Ohta N, Kumagai T, Maruyama H, Yoshida A, He Y, Zhang R (2004) Research on calpain of Schistosoma japonicum as a vaccine candidate. Parasitol Int 53:175–181CrossRefPubMedGoogle Scholar
  26. Ren F, Zhan X, Martens G, Lee J, Center D, Hanson SK, Kornfeld H (2005) Pro-IL-16 regulation in activated murine CD4+ lymphocytes. J Immunol 174:2738–2745PubMedGoogle Scholar
  27. Shen L, Zhang C, Wang T, Brooks S, Ford RJ, Lin-Lee YC, Kasianowicz A, Kumar V, Martin L, Liang P, Cowell J, Ambrus JL Jr (2006) Development of autoimmunity in IL-14alpha-transgenic mice. J Immunol 177:5676–5686PubMedGoogle Scholar
  28. Sher A, Hieny S, James SL, Asofsky R (1982) Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. II. Analysis of immunity in hosts deficient in T lymphocytes, B lymphocytes, or complement. J Immunol 128:1880–1884PubMedGoogle Scholar
  29. Siddiqui AA, Zhou Y, Podesta RB, Karcz SR, Tognon CE, Strejan GH, Dekaban GA, Clarke MW (1993) Characterization of Ca(2+)-dependent neutral protease (calpain) from human blood flukes, Schistosoma mansoni. Biochim Biophys Acta 1181:37–44PubMedGoogle Scholar
  30. Siddiqui AA, Phillips T, Charest H, Podesta RB, Quinlin ML, Pinkston JR, Lloyd JD, Paz M, Villalovos RM, Pompa J (2003a) Induction of protective immunity against Schistosoma mansoni via DNA priming and boosting with the large subunit of calpain (Sm-p80): adjuvant effects of granulocyte-macrophage colony-stimulating factor and interleukin-4. Infect Immun 71:3844–3851CrossRefPubMedGoogle Scholar
  31. Siddiqui AA, Phillips T, Charest H, Podesta RB, Quinlin ML, Pinkston JR, Lloyd JD, Pompa J, Villalovos RM, Paz M (2003b) 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 20(21):2882–2889CrossRefGoogle Scholar
  32. Siddiqui AA, Pinkston JR, Quinlin ML, Kavikondala V, Rewers-Felkins KA, Phillips T, Pompa J (2005a) Characterization of protective immunity induced against Schistosoma mansoni via DNA priming with the large subunit of calpain (Sm-p80) in the presence of genetic adjuvants. Parasite 12:3–8PubMedGoogle Scholar
  33. Siddiqui AA, Pinkston JR, Quinlin ML, Saeed Q, White GL, Shearer MH, Kennedy RC (2005b) Characterization of the immune response to DNA vaccination strategies for schistosomiasis candidate antigen, Sm-p80 in the baboon. Vaccine 23:1451–1456CrossRefPubMedGoogle Scholar
  34. Siddiqui AA, Ahmad G, Damian RT, Kennedy RC (2008) Experimental vaccines in animal models for schistosomiasis. Parasitol Res 102:825–833CrossRefPubMedGoogle Scholar
  35. Silva EE, Clarke MW, Podesta RB (1993) Characterization of a C3 receptor on the envelope of Schistosoma mansoni. J Immunol 151:7057–7066PubMedGoogle Scholar
  36. Smith JK, Siddiqui AA, Modica LA, Dykes R, Simmons C, Schmidt J, Krishnaswamy GA, Berk SL (1999) Interferon-alpha upregulates gene expression of aquaporin-5 in human parotid glands. J Interferon Cytokine Res 19:929–935CrossRefPubMedGoogle Scholar
  37. Steinmann P, Keiser J, Bos R, Tanner M, Utzinger J (2006) Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infect Dis 6:411–425CrossRefPubMedGoogle Scholar
  38. Tallima H, Salah M, Guirguis FR, El RR (2009) Transforming growth factor-beta and Th17 responses in resistance to primary murine schistosomiasis mansoni. Cytokine (in press)Google Scholar
  39. Utzinger J, Keiser J, Shuhua X, Tanner M, Singer BH (2003) Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials. Antimicrob Agents Chemother 47:1487–1495CrossRefPubMedGoogle Scholar
  40. van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD, Engels D (2003) Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Trop 86:125–139CrossRefPubMedGoogle Scholar
  41. Wilson MS, Mentink-Kane MM, Pesce JT, Ramalingam TR, Thompson R, Wynn TA (2007) Immunopathology of schistosomiasis. Immunol Cell Biol 85:148–154CrossRefPubMedGoogle Scholar
  42. Wilson RA, Langermans JA, Van Dam GJ, Vervenne RA, Hall SL, Borges WC, Dillon GP, Thomas AW, Coulson PS (2008) Elimination of Schistosoma mansoni adult worms by rhesus macaques: basis for a therapeutic vaccine? PLoS Negl Trop Dis 2:e290CrossRefPubMedGoogle Scholar
  43. Yoshida M, Kezuka T, Streilein JW (2000) Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 2. Generation of TGF-beta-producing regulatory T cells. Invest Ophthalmol Vis Sci 41:3862–3870PubMedGoogle Scholar
  44. Young BW, Podesta RB (1986) Complement and 5-HT increase phosphatidylcholine incorporation into the outer bilayers of Schistosoma mansoni. J Parasitol 72:802–803CrossRefPubMedGoogle Scholar
  45. Zhang R, Yoshida A, Kumagai T, Kawaguchi H, Maruyama H, Suzuki T, Itoh M, El-Malky M, Ohta N (2001) Vaccination with calpain induces a Th1-biased protective immune response against Schistosoma japonicum. Infect Immun 69:386–391CrossRefPubMedGoogle Scholar
  46. Zhou Y, Podesta RB (1989) Effects of serotonin (5HT) and complement C3 on the synthesis of the surface membrane precursors of adult Schistosoma mansoni. J Parasitol 75:333–343CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Gul Ahmad
    • 1
  • Weidong Zhang
    • 1
  • Workineh Torben
    • 1
  • Chad Haskins
    • 1
  • Sue Diggs
    • 1
  • Zahid Noor
    • 1
  • Loc Le
    • 1
  • Afzal A. Siddiqui
    • 1
    • 2
  1. 1.Department of Microbiology and ImmunologyTexas Tech University Health Sciences CenterLubbockUSA
  2. 2.Department of Internal MedicineTexas Tech University Health Sciences CenterLubbockUSA

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