Volume 80, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


An attempt was made to study the immunoprophylactic efficacy of recombinant transglutaminase (BmTGA) as protein vaccine along with two other recombinant proteins, abundant larval transcript-2 (BmALT-2) and thioredoxin peroxidase (BmTPX), in single and multiple antigen form for human lymphatic filariasis. Parasite challenge studies in jirds exhibited protection of 30%, 69%, and 43% against BmTGA, BmALT-2, and BmTPX, respectively, in single antigen vaccination mode. The protective efficacy of BmTGA was enhanced significantly (74%) by immunizing the jirds in multiple antigen vaccination mode along with BmTPX, whereas immunizing with the combination of BmTGA and BmALT2 conferred only 47% protection. The same protection profiles were obtained by antibody–dependent cellular cytotoxicity, using live microfilariae and L3 stage larvae. The immune response was Th2 biased, irrespective of single or multiple vaccinations. The combination of BmTGA and BmTPX seems to be a promising vaccine candidate against lymphatic filariasis.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. World Health Organisation, 2006. Global Programme to Eliminate Lymphatic Filariasis. Wkly Epidemiol Rec 22 : 221–232. [Google Scholar]
  2. Maizels RM, Balxter ML, Scott AL, 2001. Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity. Parasite Immunol 23 : 327–344. [Google Scholar]
  3. Lucius R, Textor G, Kern A, Kirsten C, 1991. Acanthocheilonema viteae: vaccination of jirds with irradiation-attenuated stage-3 larvae and with exported larval antigens. Exp Parasitol 73 : 184–196. [Google Scholar]
  4. Yates JA, Higashi GI, 1985. Brugia malayi: vaccination of jirds with 60cobalt-attenuated infective stage larvae protects against homologous challenge. Am J Trop Med Hyg 34 : 1132–1137. [Google Scholar]
  5. Mehta K, Chandrashekar R, Rao UR, 1996. Transglutaminase-catalyzed incorporation of host proteins in Brugia malayi microfilariae. Mol Biochem Parasitol 76 : 105–114. [Google Scholar]
  6. Coler RN, Reed SG, 2005. Second-generation vaccines against leishmaniasis. Trends Parasitol 21 : 244–249. [Google Scholar]
  7. Dupre Herv M, Schacht AM, Capron A, Riveau G, 1999. Control of Schistosomiasis pathology by combination of Sm28GST DNA immunization and praziquantel treatment. J Infect Dis 180 : 454–463. [Google Scholar]
  8. Kedzierski L, Black CG, Goschnick MW, Stowers AW, Coppel RL, 2002. Immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with Plasmodium yoelii. Infect Immun 70 : 6606–6613. [Google Scholar]
  9. Cookson E, Blaxter ML, Selkirk ME, 1992. Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase. Proc Natl Acad Sci USA 89 : 5837–5841. [Google Scholar]
  10. Smith DB, Davern KM, Board PG, Tiu WU, Garcia EG, Mitchell GF, 1986. Mw 26,000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase. Proc Natl Acad Sci USA 83 : 8703–8707. [Google Scholar]
  11. Ghosh I, Eisinger SW, Raghavan N, Scott AL, 1998. Thioredoxin peroxidases from Brugia malayi. Mol Biochem Parasitol 91 : 207–220. [Google Scholar]
  12. Klimowski L, Chandrashekar R, Tripp CA, 1997. Molecular cloning, expression and enzymatic activity of a thioredoxin peroxidase from Dirofilaria immitis. Mol Biochem Parasitol 90 : 297–306. [Google Scholar]
  13. Gnanasekar M, Rao KV, He YX, Mishra PK, Nutman TB, Kaliraj P, Ramaswamy K, 2004. Novel phage display-based subtractive screening to identify vaccine candidates of Brugia malayi. Infect Immun 72 : 4707–4715. [Google Scholar]
  14. Gregory WF, Atmadja AK, Allen JE, Maizels RM, 2000. The abundant larval transcript -1 and -2 genes of Brugia malayi encode stage-specific candidate vaccine antigens for filariasis. Infect Immun 68 : 4174–4179. [Google Scholar]
  15. Ramachandran S, Kumar MP, Rami RM, Chinnaiah HB, Nutman T, Kaliraj P, McCarthy J, 2004. The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination. Microbiol Immunol 48 : 945–955. [Google Scholar]
  16. Uma V, Geetha M, Murugan V, Kaliraj P, 2006. Isolation and characterization of recombinant Brugian parasitic transglutaminase. Indian J Biotechnol 5 : 317–326. [Google Scholar]
  17. Slaughter TF, Achyuthan KE, Lai TS, Greenberg CS, 1992. A microtiter plate transglutaminase assay utilizing 5-(biotin-amido)pentylamine as substrate. Anal Biochem 15 : 66–71. [Google Scholar]
  18. Suzuki T, Seregeg IG, 1979. A mass dissection technique for determining infectivity rate of filariasis vectors. Jpn J Exp Med 49 : 117–121. [Google Scholar]
  19. Sänger I, Lämmler G, Kimmiq P, 1981. Filarial infections of Mastomys natalensis and their relevance for experimental chemotherapy. Acta Trop 38 : 277–288. [Google Scholar]
  20. Thirugnanam S, Pandiaraja P, Ramaswamy K, Murugan V, Gnanasekar M, Nandakumar K, Reddy MV, 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. Exp Parasitol 116 : 483–491. [Google Scholar]
  21. Chandrashekar R, Rao UR, Parab PB, Subramanyam D, 1985a. Brugia malayi: serum dependent cell mediated reactions to microfilaria. Southeast Asian J Trop Med Public Health 16 : 15–21. [Google Scholar]
  22. Chandrashekar R, Rao UR, Subramanyam D, 1985b. Serum dependent cell mediated reactions to Brugia phangi infective larvae. Parasite Immunol 7 : 633–642. [Google Scholar]
  23. World Health Organization, 1992. Lymphatic filariasis: the disease and its control. Fifth report of the WHO Expert Committee on Filariasis. World Health Organ Tech Rep Ser 821 : 1–71. [Google Scholar]
  24. Geldhof P, De Maere V, Vercruysse J, Claerebout E, 2007. Recombinant expression systems: the obstacle to helminth vaccines? Trends Parasitol 23 : 527–532. [Google Scholar]
  25. Folk JE, 1983. Mechanism and basis for specificity of trans-glutaminase-catalyzed epsilon-(gamma-glutamyl) lysine bond formation. Adv Enzymol Relat Areas Mol Biol 54 : 1–56. [Google Scholar]
  26. Chandrashekar R, Tsuji N, Morales T, Ozols V, Mehta K, 1998. An ERp60-like protein from the filarial parasite Dirofilaria immitis has both transglutaminase and protein disulfide isomerase activity. Proc Natl Acad Sci USA 95 : 531–536. [Google Scholar]
  27. Lustigman S, Brotman B, Huima T, Castelhano AL, Singh RN, Mehta K, Prince AM, 1995. Transglutaminase-catalyzed reaction is important for molting of Onchocerca volvulus third-stage larvae. Antimicrob Agents Chemother 39 : 1913–1919. [Google Scholar]
  28. Rao UR, Mehta K, Subrahmanyam D, Vickery AC, 1991. Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro. Antimicrob Agents Chemother 35 : 2219–2224. [Google Scholar]
  29. Adini A, Krugliak M, Ginsburg H, Li L, Lavie L, Warburg A, 2001. Transglutaminase in Plasmodium parasites: activity and putative role in oocysts and blood stages. Mol Biochem Parasitol 2 : 161–168. [Google Scholar]
  30. Maizels RM, Lawrence R, 1991. Immunological tolerance: the key feature in human filariasis? Parasitol Today 7 : 271–276. [Google Scholar]
  31. Burns JM Jr, Flaherty PR, Romero MM, Weidanz WP, 2003. Immunization against Plasmodium chabaudi malaria using combined formulations of apical membrane antigen-1 and merozoite surface protein-1. Vaccine 21 : 1843–1852. [Google Scholar]
  32. Shi Q, Lynch MM, Romero M, Burns JM Jr, 2007. Enhanced protection against malaria by a chimeric merozoite surface protein vaccine. Infect Immun 75 : 1349–1358. [Google Scholar]
  33. Lu W, Egerton GL, Bianco AE, Williams SA, 1998. Thioredoxin peroxidase from Onchocerca volvulus: a major hydrogen peroxide detoxifying enzyme in filarial parasites. Mol Biochem Parasitol 91 : 221–235. [Google Scholar]
  34. Ash LR, Riley JM, 1970. Development of subperiodic Brugia malayi in the jird, Meriones unguiculatus, with notes on infections in other rodents. J Parasitol 56 : 969–973. [Google Scholar]
  35. Artis D, 2006. New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes. Int J Parasitol 36 : 723–733. [Google Scholar]
  36. Rao RU, Mehta K, 2004. Transglutaminases, thioredoxins and protein disulphide isomerase: diverse enzymes with a common goal of cross-linking proteins in lower organisms. Indian J Exp Biol 42 : 235–243. [Google Scholar]
  37. Kurniawan A, Yazdanbakhsh M, Ree RA, Aalberse R, Selkirk ME, Partono F, Maizels RM, 1993. Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic filariasis. J Immunol 150 : 3941–3950. [Google Scholar]

Data & Media loading...

  • Received : 10 Aug 2008
  • Accepted : 24 Sep 2008

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error