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A DNA vaccine co-expressing Trichinella spiralis MIF and MCD-1 with murine ubiquitin induces partial protective immunity in mice

Published online by Cambridge University Press:  05 January 2012

F. Tang ,
L. Xu ,
R. Yan ,
X. Song  and
X. Li
F. Tang
Affiliation:
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
L. Xu
Affiliation:
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
R. Yan
Affiliation:
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
X. Song
Affiliation:
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
X. Li*
Affiliation:
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
*
* Fax: +86 25 84399000, E-mail: [email protected]
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Abstract

Co-expression of Trichinella spiralis macrophage migration inhibitory factor (TsMIF) with T. spiralis cystatin-like domain protein (TsMCD-1) in a DNA vaccine induces a Th1 immune response and partial protection against T. spiralis infection. The present study evaluated whether co-expression of mouse ubiquitin (Ub) with TsMIF and TsMCD-1 might improve the immune response against T. spiralis infection. Groups of BALB/c mice were immunized twice at 2-week intervals with 100 μg of plasmid DNA encoding either a TsMIF–TsMCD-1 fusion protein (pVAX1-Tsmif-Tsmcd-1) or an Ub-co-expressing triple fusion protein Ub–TsMIF–TsMCD-1 (pVAX1-Ub-Tsmif-Tsmcd-1). Control animals were immunized with pVAX1-Ub or blank vector plasmid. Specific antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, IgA, IgE) against the recombinant protein TsMIF–TsMCD-1, serum cytokines (interferon (IFN)-γ, interleukin (IL)-4, IL-5, transforming growth factor (TGF)-β1 and IL-17), CD4+/CD8+ T cells and cytotoxic T lymphocyte (CTL) responses were monitored. Challenge infection was performed 2 weeks after the second immunization and worm burden was assayed at 35 days post-challenge. Antibody responses induced by pVAX1-Ub-Tsmif-Tsmcd-1 were significantly lower than for TsMIF-TsMCD-1, but the vaccine induced increased levels of Th1 cytokine (IFN-γ) and increased T-cell cytotoxicity. The reduction of worm burden (37.95%) following immunization with pVAX1-Ub-Tsmif-Tsmcd-1 was significantly greater than that induced by the pVAX1-Tsmif-Tsmcd-1 vaccine (23.17%; P< 0.05).

Type
Research Papers
Information
Journal of Helminthology , Volume 87 , Issue 1 , March 2013 , pp. 24 - 33
Copyright
Copyright © Cambridge University Press 2012

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References

Bautista-Garfias, C.R., Ixta, O., Orduna, M., Martinez, F., Aguilar, B. & Cortes, A. (1999) Enhancement of resistance in mice treated with Lactobacillus casei: effect on Trichinella spiralis infection. Veterinary Parasitology 80, 251–260.CrossRefGoogle ScholarPubMed
Chou, B., Hiromatsu, K., Hisaeda, H., Duan, X., Imai, T., Murata, S., Tanaka, K. & Himeno, K. (2010) Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi. Biochemical and Biophysical Research Communications 392, 277–282.CrossRefGoogle ScholarPubMed
Dantuma, N.P., Lindsten, K., Glas, R., Jellne, M. & Masucci, M.G. (2000) Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nature Biotechnology 18, 538–543.CrossRefGoogle ScholarPubMed
Dea-Ayuela, M.A., Rama-Iniguez, S. & Bolas-Fernandez, F. (2006) Vaccination of mice against intestinal Trichinella spiralis infections by oral administration of antigens microencapsulated in methacrilic acid copolymers. Vaccine 24, 2772–2780.CrossRefGoogle ScholarPubMed
Delogu, G., Howard, A., Collins, F.M. & Morris, S.L. (2000) DNA vaccination against tuberculosis: expression of a ubiquitin-conjugated tuberculosis protein enhances antimycobacterial immunity. Infection and Immunity 68, 3097–3102.CrossRefGoogle ScholarPubMed
Fabre, M.V., Beiting, D.P., Bliss, S.K. & Appleton, J.A. (2009) Immunity to Trichinella spiralis muscle infection. Veterinary Parasitology 159, 245–248.CrossRefGoogle ScholarPubMed
Finkelman, F.D., Shea-Donohue, T., Morris, S.C., Gildea, L., Strait, R., Madden, K.B., Schopf, L. & Urban, J.F. Jr. (2004) Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunological Reviews 201, 139–155.CrossRefGoogle Scholar
Finley, D. (2009) Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annual Review of Biochemistry 78, 477–513.CrossRefGoogle ScholarPubMed
Frigerio, L., Jolliffe, N.A., Di Cola, A., Felipe, D.H., Paris, N., Neuhaus, J.M., Lord, J.M., Ceriotti, A. & Roberts, L.M. (2001) The internal propeptide of the ricin precursor carries a sequence-specific determinant for vacuolar sorting. Plant Physiology 126, 167–175.CrossRefGoogle ScholarPubMed
Froscher, W., Gullotta, F., Saathoff, M. & Tackmann, W. (1988) Chronic trichinosis, Clinical, bioptic, serological and electromyographic observations. European Neurology 28, 221–226.Google ScholarPubMed
Gaczynska, M., Rock, K.L. & Goldberg, A.L. (1993) Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature 365, 264–267.CrossRefGoogle Scholar
Gravier, R., Dory, D., Rodriguez, F., Bougeard, S., Beven, V., Cariolet, R. & Jestin, A. (2007) Immune and protective abilities of ubiquitinated and non-ubiquitinated pseudorabies virus glycoproteins. Acta Virologica 51, 35–45.Google Scholar
Hershko, A. & Ciechanover, A. (1998) The ubiquitin system. Annual Review of Biochemistry 67, 425–479.CrossRefGoogle ScholarPubMed
Hogaboam, C.M., Collins, S.M. & Blennerhassett, M.G. (1996) Effects of oral L-NAME during Trichinella spiralis infection in rats. American Journal of Physiology Gastrointestinal and Liver Physiology 271, G338–G346.CrossRefGoogle ScholarPubMed
Hou, Y.H., Chen, J., Tong, G.Z., Tian, Z.J., Zhou, Y.J., Li, G.X., Li, X., Peng, J.M., An, T.Q. & Yang, H.C. (2008) A recombinant plasmid co-expressing swine ubiquitin and the GP5 encoding-gene of porcine reproductive and respiratory syndrome virus induces protective immunity in piglets. Vaccine 26, 1438–1449.CrossRefGoogle ScholarPubMed
Hu, W., Li, F., Yang, X., Li, Z., Xia, H., Li, G., Wang, Y. & Zhang, Z. (2004) A flexible peptide linker enhances the immunoreactivity of two copies HBsAg preS1 (21-47) fusion protein. Journal of Biotechnology 107, 83–90.CrossRefGoogle ScholarPubMed
Ishikawa, N., Goyal, P.K., Mahida, Y.R., Li, K.F. & Wakelin, D. (1998) Early cytokine responses during intestinal parasitic infections. Immunology 93, 257–263.CrossRefGoogle ScholarPubMed
Johnson, E.S., Ma, P.C., Ota, I.M. & Varshavsky, A. (1995) A proteolytic pathway that recognizes ubiquitin as a degradation signal. Journal of Biological Chemistry 270, 17442–17456.CrossRefGoogle ScholarPubMed
Khan, W.I. & Collins, S.M. (2004) Immune-mediated alteration in gut physiology and its role in host defence in nematode infection. Parasite Immunology 26, 319–326.CrossRefGoogle ScholarPubMed
Kolodziej-Sobocinska, M., Dvoroznakova, E. & Dziemian, E. (2006) Trichinella spiralis: macrophage activity and antibody response in chronic murine infection. Experimental Parasitology 112, 52–62.CrossRefGoogle ScholarPubMed
Kozak, M. (1987) An analysis of 5′-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Research 15, 8125–8148.CrossRefGoogle Scholar
Michels, C.E., Scales, H.E., Saunders, K.A., McGowan, S., Brombracher, F., Alexander, J. & Lawrence, C.E. (2009) Neither interleukin-4 receptor alpha expression on CD4+ T cells, or macrophages and neutrophils is required for protective immunity to Trichinella spiralis. Immunology 128, e385–394.CrossRefGoogle ScholarPubMed
Nagano, I., Wu, Z. & Takahashi, Y. (2009) Functional genes and proteins of Trichinella spp. Parasitology Research 104, 197–207.CrossRefGoogle ScholarPubMed
Nathan, C.F., Murray, H.W., Wiebe, M.E. & Rubin, B.Y. (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. Journal of Experimental Medicine 158, 670–689.CrossRefGoogle ScholarPubMed
Ortmann, B., Androlewicz, M.J. & Cresswell, P. (1994) MHC class I/beta 2-microglobulin complexes associate with TAP transporters before peptide binding. Nature 368, 864–867.CrossRefGoogle ScholarPubMed
Pennock, J.L., Behnke, J.M., Bickle, Q.D., Devaney, E., Grencis, R.K., Isaac, R.E., Joshua, G.W., Selkirk, M.E., Zhang, Y. & Meyer, D.J. (1998) Rapid purification and characterization of L-dopachrome-methyl ester tautomerase (macrophage-migration-inhibitory factor) from Trichinella spiralis, Trichuris muris and Brugia pahangi. Biochemical Journal 335, 495–498.CrossRefGoogle ScholarPubMed
Pickart, C.M. (2001) Mechanisms underlying ubiquitination. Annual Review of Biochemistry 70, 503–533.CrossRefGoogle ScholarPubMed
Pond, L., Wassom, D.L. & Hayes, C.E. (1989) Evidence for differential induction of helper T cell subsets during Trichinella spiralis infection. Journal of Immunology 143, 4232–4237.CrossRefGoogle ScholarPubMed
Robinson, K., Bellaby, T. & Wakelin, D. (1995) Oral and parenteral vaccination against Trichinella spiralis infections in high- and low-responder mice. International Journal for Parasitology 25, 989–992.CrossRefGoogle ScholarPubMed
Robinson, M.W., Greig, R., Beattie, K.A., Lamont, D.J. & Connolly, B. (2007) Comparative analysis of the excretory-secretory proteome of the muscle larva of Trichinella pseudospiralis and Trichinella spiralis. International Journal for Parasitology 37, 139–148.CrossRefGoogle ScholarPubMed
Rodriguez, F., Zhang, J. & Whitton, J.L. (1997) DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction. Journal of Virology 71, 8497–8503.CrossRefGoogle ScholarPubMed
Suzuki, Y., Orellana, M.A., Schreiber, R.D. & Remington, J.S. (1988) Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science 240, 516–518.CrossRefGoogle ScholarPubMed
Tan, T.H., Edgerton, S.A., Kumari, R., McAlister, M.S., Roe, S.M., Nagl, S., Pearl, L.H., Selkirk, M.E., Bianco, A.E., Totty, N.F., Engwerda, C., Gray, C.A. & Meyer, D.J. (2001) Macrophage migration inhibitory factor of the parasitic nematode Trichinella spiralis. Biochemical Journal 357, 373–383.CrossRefGoogle ScholarPubMed
Tanaka, K. & Kasahara, M. (1998) The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28. Immunological Reviews 163, 161–176.CrossRefGoogle ScholarPubMed
Wakelin, D., Goyal, P.K., Dehlawi, M.S. & Hermanek, J. (1994) Immune responses to Trichinella spiralis and T. pseudospiralis in mice. Immunology 81, 475–479.Google Scholar
Wan, Q.H., Wang, J.L., He, L.F., Liu, H. & Zhang, X. (2006) Serum IL-12 level in mice infected with Trichinella spiralis. Zhongguo Ji Sheng Chong Xue Yu Ji Sheng chong Bing Za Zhi 24, 475–476.Google ScholarPubMed
Wang, Q.M., Kang, L. & Wang, X.H. (2009) Improved cellular immune response elicited by a ubiquitin-fused ESAT-6 DNA vaccine against Mycobacterium tuberculosis. Microbiology and Immunology 53, 384–390.CrossRefGoogle ScholarPubMed
Whitton, J.L., Rodriguez, F., Zhang, J. & Hassett, D.E. (1999) DNA immunization: mechanistic studies. Vaccine 17, 1612–1619.CrossRefGoogle ScholarPubMed
Wu, Z., Boonmars, T., Nagano, I., Nakada, T. & Takahashi, Y. (2003) Molecular expression and characterization of a homologue of host cytokine macrophage migration inhibitory factor from Trichinella spp. Journal of Parasitology 89, 507–515.CrossRefGoogle ScholarPubMed
Zhu, X., Long, G., Xu, F. & Gui, Y. (1993) Trichinellosis. 1st edn. pp. 258–260. Zhengzhou, Henan Science and Technology Press.Google Scholar