Hostname: page-component-745bb68f8f-kw2vx Total loading time: 0 Render date: 2025-01-11T02:52:19.553Z Has data issue: false hasContentIssue false
  • English
  • Français

Evaluation of the immune response induced by DNA vaccines expressing MIF and MCD-1 genes of Trichinella spiralis in BALB/c mice

Published online by Cambridge University Press:  25 November 2011

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: lixiangrui@njau.edu.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

Plasmids expressing macrophage migration inhibitory factor (MIF) of Trichinella spiralis (TsMIF), multi-cystatin-like domain protein (MCD-1) of T. spiralis (TsMCD-1), or co-expressing TsMIF and TsMCD-1 were constructed with a pVAX1 vector. Their ability to generate a protective immune response against T. spiralis infection was evaluated in BALB/c mice. Groups of mice were immunized twice at 2-week intervals with 100 μg of recombinant plasmids pVAX1-Tsmif, pVAX1-Tsmcd-1 or pVAX1-Tsmif-Tsmcd-1. Control animals were immunized with phosphate-buffered saline (PBS) 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) and CD4+/CD8+ T cells were monitored. Challenge infection was performed 2 weeks following the second immunization and worm burden was assayed at 35 days post-challenge. Vaccination with pVAX1-Tsmif induced moderate serum IFN-γ and increases of CD4+ and CD8+ T cells, but no specific immunoglobulin antibody response. Vaccination with pVAX1-Tsmcd-1 induced a predominant Th1 antibody (IgG2a and IgG2b) response and strong levels of serum IFN-γ, and increases of CD4+ T cells. Importantly, co-expression of TsMIF and TsMCD-1 in DNA immunization produced more serum IFN-γ and markedly enhanced CD4+ and CD8+ T cells than the single DNA vaccine of the two genes. Challenge infection demonstrated that immunization with pVAX1-Tsmif-Tsmcd-1 reduced worm burdens (by 23.17%; P < 0.05).

Type
Research Papers
Information
Journal of Helminthology , Volume 86 , Issue 4 , December 2012 , pp. 430 - 439
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Augustijn, K.D., Kleemann, R., Thompson, J., Kooistra, T., Crawford, C.E., Reece, S.E., Pain, A., Siebum, A.H., Janse, C.J. & Waters, A.P. (2007) Functional characterization of the Plasmodium falciparum and P. berghei homologues of macrophage migration inhibitory factor. Infection and Immunity 75, 1116–1128.CrossRefGoogle ScholarPubMed
Bacher, M., Metz, C.N., Calandra, T., Mayer, K., Chesney, J., Lohoff, M., Gemsa, D., Donnelly, T. & Bucala, R. (1996) An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proceedings of the the National Academy of Sciences of the United States of America 93, 7849–7854.Google ScholarPubMed
Beghetto, E., Nielsen, H.V., Del Porto, P., Buffolano, W., Guglietta, S., Felici, F., Petersen, E. & Gargano, N. (2005) A combination of antigenic regions of Toxoplasma gondii microneme proteins induces protective immunity against oral infection with parasite cysts. Journal of Infectious Diseases 191, 637–645.CrossRefGoogle ScholarPubMed
Chen, Z. & O'Shea, J.J. (2008) Th17 cells: a new fate for differentiating helper T cells. Immunologic Research 41, 87–102.CrossRefGoogle ScholarPubMed
Cho, Y., Jones, B.F., Vermeire, J.J., Leng, L., DiFedele, L., Harrison, L.M., Xiong, H., Kwong, Y.K., Chen, Y., Bucala, R., Lolis, E. & Cappello, M. (2007) Structural and functional characterization of a secreted hookworm Macrophage Migration Inhibitory Factor (MIF) that interacts with the human MIF receptor CD74. Journal of Biological Chemistry 282, 23447–23456.CrossRefGoogle ScholarPubMed
Cordery, D.V., Kishore, U., Kyes, S., Shafi, M.J., Watkins, K.R., Williams, T.N., Marsh, K. & Urban, B.C. (2007) Characterization of a Plasmodium falciparum macrophage-migration inhibitory factor homologue. Journal of Infectious Diseases 195, 905–912.CrossRefGoogle ScholarPubMed
Dainichi, T., Maekawa, Y., Ishii, K., Zhang, T., Nashed, B.F., Sakai, T., Takashima, M. & Himeno, K. (2001) Nippocystatin, a cysteine protease inhibitor from Nippostrongylus brasiliensis, inhibits antigen processing and modulates antigen-specific immune response. Infection and Immunity 69, 7380–7386.CrossRefGoogle ScholarPubMed
Deville, S., Pooter, A., Aucouturier, J., Laine-Prade, V., Cote, M., Boireau, P. & Vallee, I. (2005) Influence of adjuvant formulation on the induced protection of mice immunized with total soluble antigen of Trichinella spiralis. Veterinary Parasitology 132, 75–80.CrossRefGoogle ScholarPubMed
Fallon, P.G. & Alcami, A. (2006) Pathogen-derived immunomodulatory molecules: future immunotherapeutics? Trends in Immunology 27, 470–476.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
Fu, Y., Wang, W., Tong, J., Pan, Q., Long, Y., Qian, W. & Hou, X. (2009) Th17: a new participant in gut dysfunction in mice infected with Trichinella spiralis. Mediators of Inflammation 2009, 517052.CrossRefGoogle ScholarPubMed
Fulop, M., Mastroeni, P., Green, M. & Titball, R.W. (2001) Role of antibody to lipopolysaccharide in protection against low- and high-virulence strains of Francisella tularensis. Vaccine 19, 4465–4472.CrossRefGoogle ScholarPubMed
Gorelik, L., Fields, P.E. & Flavell, R.A. (2000) Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression. Journal of Immunology 165, 4773–4777.CrossRefGoogle ScholarPubMed
Gorelik, L., Constant, S. & Flavell, R.A. (2002) Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. Journal of Experimental Medicine 195, 1499–1505.CrossRefGoogle ScholarPubMed
Gregory, W.F. & Maizels, R.M. (2008) Cystatins from filarial parasites: evolution, adaptation and function in the host–parasite relationship. International Journal of Biochemistry & Cell Biology 40, 1389–1398.CrossRefGoogle ScholarPubMed
Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M. & Weaver, C.T. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunology 6, 1123–1132.CrossRefGoogle Scholar
Hartmann, S. & Lucius, R. (2003) Modulation of host immune responses by nematode cystatins. International Journal for Parasitology 33, 1291–1302.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
Inaba, T., Sato, H. & Kamiya, H. (2003a) Impeded establishment of the infective stage of Trichinella in the intestinal mucosa of mice by passive transfer of an IgA monoclonal antibody. Journal of Veterinary Medical Science 65, 1227–1231.CrossRefGoogle ScholarPubMed
Inaba, T., Sato, H. & Kamiya, H. (2003b) Monoclonal IgA antibody-mediated expulsion of Trichinella from the intestine of mice. Parasitology 126, 591–598.CrossRefGoogle ScholarPubMed
Kamir, D., Zierow, S., Leng, L., Cho, Y., Diaz, Y., Griffith, J., McDonald, C., Merk, M., Mitchell, R.A., Trent, J., Chen, Y., Kwong, Y.K., Xiong, H., Vermeire, J., Cappello, M., McMahon-Pratt, D., Walker, J., Bernhagen, J., Lolis, E. & Bucala, R. (2008) A Leishmania ortholog of macrophage migration inhibitory factor modulates host macrophage responses. Journal of Immunology 180, 8250–8261.CrossRefGoogle ScholarPubMed
Kleemann, R., Hausser, A., Geiger, G., Mischke, R., Burger-Kentischer, A., Flieger, O., Johannes, F.J., Roger, T., Calandra, T., Kapurniotu, A., Grell, M., Finkelmeier, D., Brunner, H. & Bernhagen, J. (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature 408, 211–216.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
Kutzler, M.A. & Weiner, D.B. (2008) DNA vaccines: ready for prime time? Nature Reviews Genetics 9, 776–788.CrossRefGoogle ScholarPubMed
Lettesjo, H., Ridderstad, A. & Moller, E. (1997) IgG2b inducing factor from rheumatoid arthritis synovial fluid synergizes with transforming growth factor-beta in promoting IgG2b antibody production in mouse B lymphocytes. Scandinavian Journal of Immunology 45, 50–54.CrossRefGoogle ScholarPubMed
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, 37–43.CrossRefGoogle ScholarPubMed
Lustigman, S., Brotman, B., Huima, T., Prince, A.M. & McKerrow, J.H. (1992) Molecular cloning and characterization of onchocystatin, a cysteine proteinase inhibitor of Onchocerca volvulus. Journal of Biological Chemistry 267, 17339–17346.CrossRefGoogle ScholarPubMed
Macpherson, A.J., McCoy, K.D., Johansen, F.E. & Brandtzaeg, P. (2008) The immune geography of IgA induction and function. Mucosal Immunology 1, 11–22.CrossRefGoogle ScholarPubMed
Martinez-Gomez, F., Santiago-Rosales, R. & Ramon Bautista-Garfias, C. (2009) Effect of Lactobacillus casei Shirota strain intraperitoneal administration in CD1 mice on the establishment of Trichinella spiralis adult worms and on IgA anti-T. spiralis production. Veterinary Parasitology 162, 171–175.CrossRefGoogle ScholarPubMed
McIntyre, T.M., Klinman, D.R., Rothman, P., Lugo, M., Dasch, J.R., Mond, J.J. & Snapper, C.M. (1993) Transforming growth factor beta 1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells. Journal of Experimental Medicine 177, 1031–1037.CrossRefGoogle ScholarPubMed
Meyer-Siegler, K.L., Leifheit, E.C. & Vera, P.L. (2004) Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells. BMC Cancer 4, 34.CrossRefGoogle ScholarPubMed
Murray, J., Manoury, B., Balic, A., Watts, C. & Maizels, R.M. (2005) Bm-CPI-2, a cystatin from Brugia malayi nematode parasites, differs from Caenorhabditis elegans cystatins in a specific site mediating inhibition of the antigen-processing enzyme AEP. Molecular and Biochemical Parasitology 139, 197–203.CrossRefGoogle Scholar
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
Newlands, G.F., Skuce, P.J., Knox, D.P. & Smith, W.D. (2001) Cloning and expression of cystatin, a potent cysteine protease inhibitor from the gut of Haemonchus contortus. Parasitology 122, 371–378.CrossRefGoogle ScholarPubMed
Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q. & Dong, C. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunology 6, 1133–1141.CrossRefGoogle ScholarPubMed
Pastrana, D.V., Raghavan, N., FitzGerald, P., Eisinger, S.W., Metz, C., Bucala, R., Schleimer, R.P., Bickel, C. & Scott, A.L. (1998) Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor. Infection and Immunity 66, 5955–5963.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
Prieto-Lafuente, L., Gregory, W.F., Allen, J.E. & Maizels, R.M. (2009) MIF homologues from a filarial nematode parasite synergize with IL-4 to induce alternative activation of host macrophages. Journal of Leukocyte Biology 85, 844–854.CrossRefGoogle ScholarPubMed
Racine, R. & Winslow, G.M. (2009) IgM in microbial infections: taken for granted? Immunology Letters 125, 79–85.CrossRefGoogle ScholarPubMed
Reiterova, K., Antolova, D. & Hurnikova, Z. (2009) Humoral immune response of mice infected with low doses of Trichinella spiralis muscle larvae. Veterinary Parasitology 159, 232–235.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., Massie, D.H. & Connolly, B. (2007) Secretion and processing of a novel multi-domain cystatin-like protein by intracellular stages of Trichinella spiralis. Molecular and Biochemical Parasitology 151, 9–17.CrossRefGoogle ScholarPubMed
Salinas-Carmona, M.C. & Perez-Rivera, I. (2004) Humoral immunity through immunoglobulin M protects mice from an experimental actinomycetoma infection by Nocardia brasiliensis. Infection and Immunity 72, 5597–5604.CrossRefGoogle ScholarPubMed
Savitt, A.G., Mena-Taboada, P., Monsalve, G. & Benach, J.L. (2009) Francisella tularensis infection-derived monoclonal antibodies provide detection, protection, and therapy. Clinical and Vaccine Immunology 16, 414–422.CrossRefGoogle ScholarPubMed
Shao, D., Han, Z., Lin, Y., Zhang, L., Zhong, X., Feng, M., Guo, Y. & Wang, H. (2008) Detection of Plasmodium falciparum derived macrophage migration inhibitory factor homologue in the sera of malaria patients. Acta Tropica 106, 9–15.CrossRefGoogle ScholarPubMed
Shao, D., Zhong, X., Zhou, Y.F., Han, Z., Lin, Y., Wang, Z., Bu, L., Zhang, L., Su, X.D. & Wang, H. (2010) Structural and functional comparison of MIF ortholog from Plasmodium yoelii with MIF from its rodent host. Molecular Immunology 47, 726–737.CrossRefGoogle ScholarPubMed
Solis, C.F., Ostoa-Saloma, P., Lugo-Martinez, V.H., Johnston, S.A. & Laclette, J.P. (2005) Genetic vaccination against murine cysticercosis by using a plasmid vector carrying Taenia solium paramyosin. Infection and Immunity 73, 1895–1897.CrossRefGoogle ScholarPubMed
Song, X., Xu, L., Yan, R., Huang, X., Shah, M.A. & Li, X. (2009) The optimal immunization procedure of DNA vaccine pcDNA-TA4-IL-2 of Eimeria tenella and its cross-immunity to Eimeria necatrix and Eimeria acervulina. Veterinary Parasitology 159, 30–36.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
Sykes, K. (2008) Progress in the development of genetic immunization. Expert Review of Vaccines 7, 1395–1404.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
Vermeire, J.J., Cho, Y., Lolis, E., Bucala, R. & Cappello, M. (2008) Orthologs of macrophage migration inhibitory factor from parasitic nematodes. Trends in Parasitology 24, 355–363.CrossRefGoogle ScholarPubMed
Wallach, M.G., Mencher, D., Yarus, S., Pillemer, G., Halabi, A. & Pugatsch, T. (1989) Eimeria maxima: identification of gametocyte protein antigens. Experimental Parasitology 68, 49–56.CrossRefGoogle ScholarPubMed
Wang, S., Zhu, X., Yang, Y., Yang, J., Gu, Y., Wei, J., Hao, R., Boireau, P. & Cui, S. (2009) Molecular cloning and characterization of heat shock protein 70 from Trichinella spiralis. Acta Tropica 110, 46–51.CrossRefGoogle ScholarPubMed
Wei, J., Gu, Y., Yang, J., Yang, Y., Wang, S., Cui, S. & Zhu, X. (2011) Identification and characterization of protective epitope of Trichinella spiralis paramyosin. Vaccine 29, 3162–3168.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
Xu, Q., Song, X., Xu, L., Yan, R., Shah, M.A. & Li, X. (2008) Vaccination of chickens with a chimeric DNA vaccine encoding Eimeria tenella TA4 and chicken IL-2 induces protective immunity against coccidiosis. Veterinary Parasitology 156, 319–323.CrossRefGoogle ScholarPubMed
Yang, J., Yang, Y., Gu, Y., Li, Q., Wei, J., Wang, S., Boireau, P. & Zhu, X. (2008) Identification and characterization of a full-length cDNA encoding paramyosin of Trichinella spiralis. Biochemical and Biophysical Research Communications 365, 528–533.CrossRefGoogle ScholarPubMed
Yang, J., Gu, Y., Yang, Y., Wei, J., Wang, S., Cui, S., Pan, J., Li, Q. & Zhu, X. (2010) Trichinella spiralis: immune response and protective immunity elicited by recombinant paramyosin formulated with different adjuvants. Experimental Parasitology 124, 403–408.CrossRefGoogle ScholarPubMed
Yang, Y., Zhang, Z., Yang, J., Chen, X., Cui, S. & Zhu, X. (2010) Oral vaccination with Ts87 DNA vaccine delivered by attenuated Salmonella typhimurium elicits a protective immune response against Trichinella spiralis larval challenge. Vaccine 28, 2735–2742.CrossRefGoogle ScholarPubMed
Zang, X., Taylor, P., Wang, J.M., Meyer, D.J., Scott, A.L., Walkinshaw, M.D. & Maizels, R.M. (2002) Homologues of human macrophage migration inhibitory factor from a parasitic nematode. Gene cloning, protein activity, and crystal structure. Journal of Biological Chemistry 277, 44261–44267.CrossRefGoogle ScholarPubMed
Zhu, X.Q., Long, G.X., Xu, F.H. & Gui, Y.Z. (1993) Trichinellosis. 1st edn. pp. 258–260. Zhengzhou, Henan Science and Technology Press.Google Scholar