title: Tandem antioxidant enzymes confer synergistic protective responses in experimental filariasis.
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 Mastomys coucha 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.
authors.affiliation: Centre for Biotechnology, Anna University,Chennai600025,India.
authors.forename: P R
authors.initials: PR
authors.lastname: Prince
authors.affiliation: Centre for Biotechnology, Anna University,Chennai600025,India.
authors.forename: J
authors.initials: J
authors.lastname: Madhumathi
authors.affiliation: Centre for Biotechnology, Anna University,Chennai600025,India.
authors.forename: G
authors.initials: G
authors.lastname: Anugraha
authors.affiliation: Centre for Biotechnology, Anna University,Chennai600025,India.
authors.forename: P J
authors.initials: PJ
authors.lastname: Jeyaprita
authors.affiliation: Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences,Sevagram442102,India.
authors.forename: M V R
authors.initials: MV
authors.lastname: Reddy
authors.affiliation: Centre for Biotechnology, Anna University,Chennai600025,India.
authors.forename: P
authors.initials: P
authors.lastname: Kaliraj
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D000975:Antioxidants / Q000378:metabolism*; D005260:Female; D005368:Filariasis / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051189:Murinae; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins; D013879:Thioredoxins / Q000276:immunology / Q000378:metabolism*; D014958:Wuchereria bancrofti / Q000201:enzymology*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D000975:Antioxidants; D011994:Recombinant Proteins; D013879:Thioredoxins; D054464:Peroxiredoxins