Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-19T06:04:41.380Z Has data issue: false hasContentIssue false
  • English
  • Français

Tandem antioxidant enzymes confer synergistic protective responses in experimental filariasis

Published online by Cambridge University Press:  16 May 2013

P.R. Prince ,
J. Madhumathi ,
G. Anugraha ,
P.J. Jeyaprita ,
M.V.R. Reddy  and
P. Kaliraj
P.R. Prince
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
J. Madhumathi
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
G. Anugraha
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
P.J. Jeyaprita
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
M.V.R. Reddy
Affiliation:
Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram442102, India
P. Kaliraj*
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
*
*Fax:+91 44 22352642, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Helminth parasites use antioxidant defence strategies for survival during oxidative stress due to free radicals in the host. Accordingly, tissue-dwelling filarial parasites counteract host responses by releasing a number of antioxidants. Targeting these redox regulation proteins together, would facilitate effective parasite clearance. Here, we report the combined effect of protective immune responses trigged by recombinant Wuchereria bancrofti thioredoxin (WbTRX) and thioredoxin peroxidase (WbTPX) in an experimental filarial model. The expression of WbTRX and WbTPX in different stages of the parasite and their cross-reactivity were analysed by enzyme-linked immunosorbent assay (ELISA). The immunogenicity of recombinant proteins and their protective efficacy were studied in animal models when immunized in single or cocktail mode. The antigens showed cross-reactive epitopes and induced high humoral and cellular immune responses in mice. Further, parasite challenge against Brugia malayi L3 larvae in Mastomyscoucha conferred significant protection of 57% and 62% against WbTRX and WbTPX respectively. The efficacy of L3 clearance was significantly higher (71%) (P <  0.001) when the antigens were immunized together, showing a synergistic effect in multiple-mode vaccination. Hence, the study suggests WbTRX and WbTPX to be attractive vaccine candidates when immunized together and provides a tandem block for parasite elimination in the control of lymphatic filariasis.

Type
Research Papers
Information
Journal of Helminthology , Volume 88 , Issue 4 , December 2014 , pp. 402 - 410
Copyright
Copyright © Cambridge University Press 2013 

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

Abraham, D., Lange, A.M., Yutanawiboonchai, W., Trpis, M., Dickerson, J.W., Swenson, B. & Eberhard, M.L. (1993) Survival and development of larval Onchocerca volvulus in diffusion chambers implanted in primate and rodent hosts. Journal of Parasitology 79, 571–582.CrossRefGoogle ScholarPubMed
Anand, S.B., Murugan, V., Prabhu, P.R., Anandharaman, V., Reddy, M.V. & Kaliraj, P. (2008) Comparison of immunogenicity, protective efficacy of single and cocktail DNA vaccine of Brugia malayi abundant larval transcript (ALT-2) and thioredoxin peroxidase (TPX) in mice. Acta Tropica 107, 106–112.Google Scholar
Anand, S.B., Kodumudi, K.N., Reddy, M.V. & Kaliraj, P. (2011) A combination of two Brugia malayi filarial vaccine candidate antigens (BmALT-2 and BmVAH) enhances immune responses and protection in jirds. Journal of Helminthology 4, 1–11.Google Scholar
Babu, S., Ganley, L.M., Klei, T.R., Shultz, L.D. & Rajan, T.V. (2000) Role of gamma interferon and interleukin-4 in host defence against the human filarial parasite Brugia malayi. Infection and Immunity 68, 3034–3035.Google Scholar
Blaxter, M., Daub, J., Guiliano, D., Parkinson, J. & Whitton, C. (2002) Filarial Genome Project. The Brugia malayi genome project: expressed sequence tags and gene discovery. Transactions of the Royal Society of Tropical Medicine and Hygiene 96, 7–17.Google Scholar
Chenthamarakshan, V., Reddy, M.V. & Harinath, B.C. (1995) Immunoprophylactic potential of a 120 kDa Brugia malayi adult antigen fraction, BmA-2, in lymphatic filariasis. Parasite Immunology 17, 277–285.Google Scholar
Chiumiento, L. & Bruschi, F. (2009) Enzymatic antioxidant systems in helminth parasites. Parasitology Research 105, 593–603.Google Scholar
Ghosh, I., Eisinger, S.W., Raghavan, N. & Scott, A.L. (1998) Thioredoxin peroxidase from Brugia malayi. Molecular Biochemical Parasitology 91, 207–220.Google Scholar
Gnanasekar, M., Rao, K.V., He, Y.X., Mishra, P.K., Nutman, T.B., Kaliraj, P., & Ramaswamy, K. (2004) Novel phage display-based subtractive screening to identify vaccine candidates of Brugia malayi. Infection and Immunity 72, 4707–4715.CrossRefGoogle ScholarPubMed
Grezel, D., Capron, M., Grzych, J.M., Fontaine, J. & Lecocq, J.P. (1993) Protective immunity induced in rat schistosomiasis by a single dose of the Sm28GST recombinant antigen: effector mechanisms involving IgE and IgA antibodies. European Journal of Immunology 4, 211–222.Google Scholar
Henkle-Dührsen, K. & Kampkötter, A. (2001) Antioxidant enzyme families in parasitic nematodes. Molecular Biochemistry and Parasitology 114, 29–42.Google Scholar
Hoerauf, A. (2006) New strategies to combat filariasis. Expert Review of Anti-Infective Therapy 4, 211–222.Google Scholar
Hoerauf, A., Satoguina, J., Saeftel, M. & Specht, S. (2005) Immunomodulation by filarial nematodes. Parasite Immunology 27, 417–429.Google Scholar
Klimowski, l., Chandrashekar, R. & Tripp, C.A. (1997) Molecular cloning, expression and enzymatic activity of a thioredoxin peroxidase from Dirofilaria immitis. Molecular and Biochemical Parasitology 90, 297–306.Google Scholar
Kunchithapautham, K., Padmavathi, B., Narayanan, R.B., Kaliraj, P. & Scott, A.L. (2003) Thioredoxin from Brugia malayi: defining a 16-Kilodalton class of thioredoxins from nematodes. Infection and Immunity 71, 4119–4126.Google Scholar
Lawrence, R.A. (2001) Immunity to filarial nematodes. Veterinary Parasitology 100, 33–44.Google Scholar
Lok, J.B. & Abraham, D. (1992) Animal models for the study of immunity in human filariasis. Parasitology Today 8, 168–171.Google Scholar
LoVerde, P.T., Carvalho-Queiroz, C. & Cook, R. (2004) Vaccination with antioxidant enzymes confers protective immunity against challenge infection with Schistosoma mansoni. Memorias do Instituto Oswaldo Cruz 99 (Suppl. I), 37–43.Google Scholar
Madhumathi, J., Prince, P.R., Anugraha, G., Kiran, P., Rao, D.N., Reddy, M.V. & Perumal, K. (2010) Identification and characterization of nematode specific protective epitopes of B. malayi TRX towards development of synthetic vaccine construct for lymphatic filariasis. Vaccine 28, 5038–5048.Google Scholar
Maizels, R.M. & Yazdanbakhsh, M. (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews Immunology 3, 733–744.Google Scholar
Martin, C., Al-Qaoud, K.M., Ungeheuer, M.N., Paehle, K., Vuong, P.N., Bain, O., Fleischer, B. & Hoerauf, A. (2000) IL-5 is essential for vaccine-induced protection and for resolution of primary infection in murine filariasis. Medical Microbiology and Immunology 189, 67–74.Google Scholar
McGonigle, S., Dalton, J.P. & James, E.R. (1998) Peroxidoxins: a new antioxidant family. Parasitology Today 14, 139–145.Google Scholar
Mendez, S., Zhan, B., Goud, G., Ghosh, K., Dobardzic, A., Wu, W., Liu, S., Deumic, V., Dobardzic, R., Liu, Y., Bethony, J. & Hotez, P.J. (2005) Effect of combining the larval antigens Ancylostoma secreted protein 2 (ASP-2) and metalloprotease 1 (MTP-1) in protecting hamsters against hookworm infection and disease caused by Ancylostoma ceylanicum. Vaccine 23, 3123–3130.Google Scholar
Rainczuk, A., Scorza, T., Spithill, T.W. & Smooker, P.M. (2004) A bicistronic DNA vaccine containing apical membrane antigen 1 and merozoite surface protein 4/5 can prime humoral and cellular immune responses and partially protect mice against virulent Plasmodium chabaudi adami DS malaria. Infection and Immunity 72, 5565–5573.Google Scholar
Rajan, B., Ramalingam, T. & Rajan, T.V. (2005) Critical role for IgM in host protection in experimental filarial infection. Journal of Immunology 175, 1827–1833.Google Scholar
Ramalingam, T., Ganley, L., Porte, P. & Rajan, T.V. (2003) Impaired clearance of primary but not secondary Brugia infections in IL-5 deficient mice. Experimental Parasitology 105, 131–139.Google Scholar
Sänger, I., Lämmler, G. & Kimmig, P. (1981) Filarial infections of Mastomys natalensis and their relevance for experimental chemotherapy. Acta Tropica 38, 277–288.Google Scholar
Suzuki, T. & Seregeg, I.G. (1979) A mass dissection technique for determining infectivity rate of filariasis vectors. Japanese Journal of Experimental Medicine 49, 117–121.Google Scholar
Thirugnanam, S., Pandiaraja, P., Ramaswamy, K., Murugan, V., Gnanasekar, M., Nandakumar, K., Reddy, M.V. & Kaliraj, P. (2007) Brugia malayi: comparison of protective immune responses induced by Bm-alt-2 DNA, recombinant Bm-ALT-2 protein and prime-boost vaccine regimens in a jird model. Experimental Parasitology 116, 483–491.Google Scholar
Vanam, U., Pandey, V., Prabhu, P.R., Dakshinamurthy, G., Reddy, M.V. & Kaliraj, P. (2009) Evaluation of immunoprophylactic efficacy of Brugia malayi transglutaminase (BmTGA) in single and multiple antigen vaccination with BmALT-2 and BmTPX for human lymphatic filariasis. American Journal of Tropical Medicine and Hygiene 80, 319–324.Google Scholar
World Health Organization, (2001) Global programme to eliminate lymphatic filariasis. WHO annual report on lymphatic filariasis. Geneva, World Health Organization.Google Scholar