Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-02T20:19:21.567Z Has data issue: false hasContentIssue false
  • English
  • Français

Immune responses generated by intramuscular DNA immunization of Brugia malayi transglutaminase (BmTGA) in mice

Published online by Cambridge University Press:  15 June 2009

UMA VANAM ,
PRINCE R. PRABHU ,
VIVEK PANDEY ,
GAJALAKSHMI DAKSHINAMURTHY ,
MARYADA VENKATA RAMI REDDY  and
KALIRAJ PERUMAL
UMA VANAM
Affiliation:
Centre for Biotechnology, Anna University, Chennai, India
PRINCE R. PRABHU
Affiliation:
Centre for Biotechnology, Anna University, Chennai, India
VIVEK PANDEY
Affiliation:
Centre for Biotechnology, Anna University, Chennai, India
GAJALAKSHMI DAKSHINAMURTHY
Affiliation:
Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, India
MARYADA VENKATA RAMI REDDY
Affiliation:
Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, India
KALIRAJ PERUMAL*
Affiliation:
Centre for Biotechnology, Anna University, Chennai, India
*
*Corresponding author: Centre for Biotechnology, Anna University, Chennai, India. Tel: +91 44 22350772. Fax: +91 44 2254229. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

An attempt was made to evaluate the immunoprophylactic efficacy of Brugia malayi transglutaminase (BmTGA) as a DNA vaccine, for human lymphatic filariasis. BmTGA was cloned and characterized in the DNA vaccine vector pVAX1. Further, the tissue distribution study of the DNA construct, pVAX-TGA was carried out in mice and the DNA vaccine was shown to be efficiently distributed to all the organs, was accessible to the immune system, and at the same time was metabolized quickly and did not pose problems of toxicity. Intramuscular immunization in mice showed significant antibody production and splenocyte proliferation upon antigenic stimulation. The immune responses were biased towards the Th1 arm, as evaluated in terms of isotype antibody distribution and cytokine profile. Thus, analysis of the humoral and cellular immune responses indicated that BmTGA is a potent immunogen. However, protection studies as determined by the micropore chamber method using live microfilarial larvae, showed that the DNA vaccine could confer only partial protection in the mouse model. We conclude that despite the induction of sufficient humoral and cellular immune responses, BmTGA as a DNA vaccine could not confer much protection against subsequent challenge and other aspects of the immune responses need to be further investigated.

Keywords

filariasisDNA vaccinetransglutaminasecytokinemicropore chamber
Type
Research Article
Information
Parasitology , Volume 136 , Issue 8 , July 2009 , pp. 887 - 894
Copyright
Copyright © Cambridge University Press 2009

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

REFERENCES

Abraham, D., Lange, A. M., Yutanawiboonchai, W., Trpis, M., Dickerson, J.W., Swenson, B. and 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
Ash, L. R. and Riley, J. M. (1970). Development of subperiodic Brugia malayi in the jird, Meriones unguiculatus, with notes on infections in other rodents. Journal of Parasitology 56, 969–973.CrossRefGoogle ScholarPubMed
Chandrashekar, R., Tsuji, N., Morales, T., Ozols, V. and Mehta, K. (1998). An ERp60-like protein from the filarial parasite Dirofilaria immitis has both transglutaminase and protein disulfide isomerase activity. Proceedings of the National Academy of Sciences, USA 95, 531–536.CrossRefGoogle ScholarPubMed
Chenthamarakshan, V., Reddy, M. V. and 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.CrossRefGoogle ScholarPubMed
Folk, J. E. (1983). Mechanism and basis for specificity of transglutaminase-catalyzed epsilon-(gamma-glutamyl) lysine bond formation. Advances in Enzymology and Related Areas of Molecular Biology 54, 1–56.Google ScholarPubMed
Gnanasekar, M., Rao, K. V., He, Y. X., Mishra, P. K., Nutman, T. B., Kaliraj, P. and Ramaswamy, K. (2004). Novel phage display-based subtractive screening to identify vaccine candidates of Brugia malayi. Infection and Immunity 72, 4707–4715.CrossRefGoogle ScholarPubMed
Grieve, R. B., Wisnewski, N., Frank, G. R. and Tripp, C. A. (1995). Vaccine research and development for the prevention of filarial nematode infections. Pharmaceutical Biotechnology 6, 737–768.CrossRefGoogle ScholarPubMed
Knox, D. P., Redmond, D. L., Skuce, P. J. and Newlands, G. F. (2001). The contribution of molecular biology to the development of vaccines against nematode and trematode parasites of domestic ruminants. Veterinary Parasitology 101, 311–335.CrossRefGoogle Scholar
Liu, C., Fan, M., Xu, Q. and Li, Y. (2008). Biodistribution and expression of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in mice. Journal of Gene Medicine 10, 298–305.CrossRefGoogle ScholarPubMed
Lustigman, S., Brotman, B., Huima, T., Castelhano, A. L., Singh, R. N., Mehta, K. and Prince, A. M. (1995). Transglutaminase-catalyzed reaction is important for molting of Onchocerca volvulus third-stage larvae. Antimicrobial Agents and Chemotherapy 39, 1913–1919.CrossRefGoogle ScholarPubMed
Lustigman, S. and McCarter, J. P. (2007). Ivermectin resistance in Onchocerca volvulus: toward a genetic basis. PLoS Neglected Tropical Diseases 1, e76.CrossRefGoogle Scholar
McCluskie, M. J., Brazolot Millan, C. L., Gramzinski, R. A., Robinson, H. L., Santoro, J. C., Fuller, J. T., Widera, G., Haynes, J. R., Purcell, R. H. and Davis, H. L. (1999). Route and method of delivery of DNA vaccine influence immune responses in mice and non-human primates. Molecular Medicine 5, 287–300.CrossRefGoogle ScholarPubMed
Mehta, K., Chandrashekar, R. and Rao, U. R. (1996). Transglutaminase-catalyzed incorporation of host proteins in Brugia malayi microfilariae. Molecular and Biochemical Parasitology 76, 105–114.CrossRefGoogle ScholarPubMed
Mehta, K., Rao, U. R., Vickery, A. C. and Fesus, L. (1992). Identification of a novel transglutaminase from the filarial parasite Brugia malayi and its role in growth and development. Molecular and Biochemical Parasitology 53, 1–15.CrossRefGoogle ScholarPubMed
Ottesen, E. A. (1985). Efficacy of diethylcarbamazine in eradicating infection with lymphatic-dwelling filariae in humans. Reviews of Infectious Diseases 7, 341–356.CrossRefGoogle ScholarPubMed
Ottesen, E. A. (2000). The global programme to eliminate lymphatic filariasis. Tropical Medicine and International Health 5, 591–594.CrossRefGoogle ScholarPubMed
Ramachandran, S., Kumar, M. P., Rami, R. M., Chinnaiah, H. B., Nutman, T., Kaliraj, P. and McCarthy, J. (2004). The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination. Microbiology and Immunology 48, 945–955.CrossRefGoogle ScholarPubMed
Rao, U. R., Mehta, K., Subrahmanyam, D. and Vickery, A. C. (1991). Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro. Antimicrobial Agents and Chemotherapy. 35, 2219–2224.CrossRefGoogle ScholarPubMed
Robinson, H. L. and Torres, C. A. (1997). DNA vaccines. Seminars in Immunology 9, 271–283.CrossRefGoogle ScholarPubMed
Sahare, K. N., Anandharaman, V., Meshram, V. G., Meshram, S. U., Gajalakshmi, D., Goswami, K. and Reddy, M. V. R. (2008). In vitro effect of four herbal plants on the motility of Brugia malayi microfilariae. Indian Journal of Medical Research 127, 467–471.Google ScholarPubMed
Suzuki, T. and Seregeg, I. G. (1979). A mass dissection technique for determining infectivity rate of filariasis vectors. Japan Journal of Experimental Medicine 49, 117–121.Google ScholarPubMed
Tang, D. C., De Vit, M. and Johnston, S. A. (1992). Genetic immunization is a simple method for eliciting an immune response. Nature, London 356, 152–154.CrossRefGoogle ScholarPubMed
Thirugnanam, S., Pandiaraja, P., Ramaswamy, K., Murugan, V., Gnanasekar, M., Nandakumar, K., Reddy, M. V. and 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.CrossRefGoogle Scholar
Uma, V., Pandey, V., Prabhu, P. R., Dakshinamurthy, G., Reddy, M. V. R. and 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
Uma, V., Geetha, M., Murugan, V. and Kaliraj, P. (2006). Isolation and characterization of recombinant Brugian parasitic transglutaminase. Indian Journal of Biotechnology 5, 317–326.Google Scholar
World Health Organization (2006). Global programme to eliminate lymphatic filariasis. Weekly Epidemiological Record 22, 221–232.Google Scholar