Acta Parasitologica

, Volume 54, Issue 3, pp 281–287 | Cite as

Vaccination of rats against the rodent hookworm Nippostrongylus brasiliensis with a recombinant superoxide dismutase fails to protect against infection

Research Note

Abstract

Anti-oxidant enzymes including superoxide dismutase (SOD) protect cells from damage by oxygen radicals produced during respiration. There is also a substantial body of evidence that anti-oxidant enzymes facilitate the survival of parasitic helminths, including gastrointestinal nematodes, within the host. Superoxide dismutase has been shown to be released by a variety of parasitic helminths and may protect them from host mediated oxidative immune responses. As it may play a parasite protective role during infections SOD has been investigated as a vaccine candidate in a range of helminth parasites including Schistosoma mansoni, Acanthocheilonema viteae and Haemonchus contortus. Here, we sought to evaluate the protective potential of SOD against the rat hookworm Nippostrongylus brasiliensis, a commonly utilised laboratory infection, as a vaccination model. A cytosolic SOD from this parasite, with high sequence homology to a putative extracellular form of the enzyme was cloned and then expressed in bacteria. The resultant recombinant protein was assessed for enzyme activity and used to immunise rats prior to a single challenge infection with the parasite. No protection was observed and monitoring systemic and mucosal antibody responses and mast cell protease levels in superoxide dismutase vaccinated rats suggested that this recombinant SOD was only weakly immunogenic.

Keywords

Nippostrongylus brasiliensis nematode hookworm superoxide dismutase recombinant vaccine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ball G., Selkirk M., Knox D.P. 2007. The effect of vaccination with a recombinant Nippostrongylus brasiliensis acetylcholinesterase on infection outcome in the rat. Vaccine, 30, 3365–3372. DOI: 10.1016/j.vaccine.2006.12.055.CrossRefGoogle Scholar
  2. Batra S., Singh S.P., Gupta S., Katiyar J.C., Srivastava V.M. 1990. Reactive oxygen intermediates metabolizing enzymes in Ancylostoma ceylanicum and Nippostrongylus brasiliensis. Free Radical Biology & Medicine, 8, 271–274. DOI: 10.1016/0891-5849(90)90074-S.CrossRefGoogle Scholar
  3. Batra S., Srivastava J.K., Gupta S., Katiyar J.C., Srivastava V.M. 1993. Role of reactive oxygen species in expulsion of Nippostrongylus brasiliensis from rats. Parasitology, 106, 185–192.PubMedCrossRefGoogle Scholar
  4. Beauchamp C., Fridovich I. 1971. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Analytical Biochemistry, 44, 276–287. DOI: 10.1016/0003-2697(71)90370-8.PubMedCrossRefGoogle Scholar
  5. Bennet-Jenkins E., Bryant C. 1996. Novel sources of anthelmintics. International Journal for Parasitology, 26, 937–947. DOI: 10.1016/S0020-7519(96)80068-3.PubMedCrossRefGoogle Scholar
  6. Britton C., Knox D.P., Kennedy M.W. 1994. Superoxide dismutase (SOD) activity of Dictyocaulus viviparus and its inhibition by antibody from infected and vaccinated bovine hosts. Parasitology, 109, 257–263.PubMedCrossRefGoogle Scholar
  7. Callahan H.L., Hazen-Martin D., Crouch R.K., James E.R. 1993. Immunolocalization of superoxide dismutase in Dirofilaria immitis adult worms. Infection and Immunity, 61, 1157–1163. DOI: 0019-9567/93/031157-07$02.00/0.PubMedGoogle Scholar
  8. Carvalho-Queiroz C., Cook R., Wang C.C., Correa-Oliveira R., Bailey N.A., Egilmez N.K., Mathiowitz E., LoVerde P.T. 2004. Cross-reactivity of Schistosoma mansoni cytosolic superoxide dismutase, a protective vaccine candidate, with host superoxide dismutase and identification of parasite-specific B epitopes. Infection and Immunity, 72, 2635–2647. DOI: 10.1128/IAI.72.5.2635-2647.2004.PubMedCrossRefGoogle Scholar
  9. Docampo R., Moreno S.N. 1986. Free radical metabolism of antiparasitic agents. Fed Proc, 45, 2471–2476.PubMedGoogle Scholar
  10. Henkle-Dührsen K., Warnecke C., Brattig N., Liebau E., Walter R.D. 1994. Characterization of enzymatically active Onchocerca volvulus Cu/Zn superoxide dismutase expressed in Escherichia coli. Molecular and Biochemical Parasitology, 67, 41–47. DOI: 10.1016/0166-6851(94)90094-9.PubMedCrossRefGoogle Scholar
  11. Holland M.J., Harcus Y.M., Riches P.L., Maizels R.M. 2000. Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses. European Journal of Immunology, 30, 1977–1987. DOI: 0014-2980/00/0707-1977$17.50+.50/0.PubMedCrossRefGoogle Scholar
  12. Jackson S. 1974. New technique for observing nematode ova from sheep faeces. Laboratory Practice, 23, 65.PubMedGoogle Scholar
  13. Jones D.G., Suttle N. 1981. Some effects of copper deficiency on leucocyte function in sheep and cattle. Research in Veterinary Science, 31, 151–156.PubMedGoogle Scholar
  14. Kennedy M., McIntosh A., Blair A., McLaughlin D. 1990. MHC (RT1) restriction of the antibody repertoire to infection with the nematode Nippostrongylus brasiliensis in the rat. Immunology, 71, 317–322.PubMedGoogle Scholar
  15. Kennedy M.W., Fraser E., Christie J. 1991. MHC class II (I-A) region control of the IgE antibody repertoire to the ABA-1 allergen of the nematode Ascaris. Immunology, 72, 577–579.PubMedGoogle Scholar
  16. Knox D.P., Jones D.G. 1992. A comparison of superoxide dismutase (SOD, EC: 1.15.1.1) distribution in gastro-intestinal nematodes. International Journal for Parasitology, 22, 209–214. DOI: 10.1016/0020-7519(92)90103-R.PubMedCrossRefGoogle Scholar
  17. Lattemann C.T., Yan Z.X., Matzen A., Meyer T.F., Apfel H. 1999. Immunogenicity of the extracellular copper/zinc superoxide dismutase of the filarial parasite Acanthocheilonema viteae delivered by a two-phase vaccine strain of Salmonella typhimurium. Parasite Immunolology, 21, 219–224.CrossRefGoogle Scholar
  18. Liddell S., Knox D.P. 1998. Extra cellular and cytoplasmic Cu/Zn superoxide dismutases from Haemonchus contortus. Parasitology, 116, 383–394.PubMedCrossRefGoogle Scholar
  19. LoVerde P.T., Carvalho-Queiroz C., Cook R. 2004. Vaccination with antioxidant enzymes confers protective immunity against challenge infection with Schistosoma mansoni. Memórias do Instituto Oswaldo Cruz, 99,(Suppl.), 37–43. DOI: 10.1590/S0074-02762004000900007.PubMedGoogle Scholar
  20. Miller H.R., Woodbury R.G., Huntley J.F., Newlands G. 1983. Systemic release of mucosal mast-cell protease in primed rats challenged with Nippostrongylus brasiliensis. Immunology, 49, 471–479. DOI: 0019-2805/83/0700-0471S02.00.PubMedGoogle Scholar
  21. Smith N.C., Bryant C. 1986. The role of host generated free radicals in helminth infections: Nippostrongylus brasiliensis and Nematospiroides dubius compared. International Journal for Parasitology, 16, 617–622.PubMedCrossRefGoogle Scholar
  22. Smith N.C., Bryant C. 1989a. Free radical generation during primary infections with Nippostrongylus brasiliensis. Parasite Immunology, 11, 147–160. DOI:10.1111/j.1365-3024.1989.tb00655.x.PubMedCrossRefGoogle Scholar
  23. Smith N.C., Bryant C. 1989b. The effect of antioxidants on the rejection of Nippostrongylus brasiliensis. Parasite Immunology, 11, 161–167. DOI:10.1111/j.1365-3024.1989.tb00656.x.PubMedCrossRefGoogle Scholar
  24. Smith N.C., Bryant C., Boreham P.F. 1988. Possible roles for pyruvate: ferredoxin oxidoreductase and thiol-dependent peroxidase and reductase activities in resistance to nitroheterocyclic drugs in Giardia intestinalis. International Journal for Parasitology, 18, 991–997. DOI: 10.1016/0020-7519(88)90183-X.PubMedCrossRefGoogle Scholar
  25. Smith N.C., Ovington K.S., Boray J.C. 1992. Fasciola hepatica: free radical generation by peritoneal leukocytes in challenged rodents. International Journal for Parasitology, 22, 281–286. DOI: 10.1016/S0020-7519(05)80005-0.PubMedCrossRefGoogle Scholar
  26. Tang L., Ou X., Henkle-Dührsen K., Selkirk M.E. 1994. Extracellular and cytoplasmic CuZn superoxide dismutases from Brugia lymphatic filarial nematode parasites. Infection and Immunity, 62, 961–967. DOI: 0019-9567/94/$04.00+0.PubMedGoogle Scholar
  27. Young C. 1996. Modulated enzyme expression in gastrointestinal nematodes. PhD Thesis, The University of Glasgow, Scotland, UK.Google Scholar

Copyright information

© © Versita Warsaw and Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of BiochemistryImperial College LondonLondonUK
  2. 2.Moredun Research InstitutePenicuikUK

Personalised recommendations