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.

Transcriptional activation of antioxidants may compensate for selenoprotein deficiencies in Amblyomma maculatum (Acari: Ixodidae) injected with selK‐ or selM‐dsRNA

“…Similarly, mice had some protection against Brugia malayi when immunized a DNA vaccine cocktail which included thioredoxin peroxidase (Anand et al 2008; Vanam et al 2009). Interestingly, there was a noted synergistic protective response when mice immunized both Wuchereria bancrofti thioredoxin and thioredoxin peroxidase in an experimental filarial model when challenged with B. malayi larvae (Prince et al 2013). A similar synergistic protective effect was noted in mice immunized against Helicobacter pylori superoxide dismutase, catalase, and thioredoxin peroxidase (Stent et al 2012).…”

“…Interestingly, antioxidant enzymes are currently being evaluated for their usefulness in developing antiparasitic drugs and as antiparasitic vaccines (Pal & Bandyopadhyay, 2012;Prince et al, 2013). A variety of inhibitors designed to target glutathione reductase or thioredoxin reductase from Plasmodium falciparum have shown marked antimalarial activity (Pal & Bandyopadhyay, 2012), which underscores the central role of the parasitic antioxidant system to the parasite's survival.…”

Evaluating the Vaccine Potential of a Tetravalent Fusion Protein (rBmHAXT) Vaccine Antigen Against Lymphatic Filariasis in a Mouse Model

“…In fact, one of our studies showed that a trivalent fusion protein rBm HAX (HSP12.6 + ALT-2 + TPX-2) vaccine conferred 67.5% protection in the mouse model ( 30 ). Immunization with TPX-2 skewed the protective immune response to a Th1 bias ( 30 , 41 , 43 ). Therefore, we hypothesized that a tetravalent fusion protein could generate a more balanced Th1/Th2 response and will be more effective as a prophylactic vaccine against LF infection.…”

Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis

“…Animals were handled in accordance with the institutional guidelines, and the experimental procedures were approved by an Institutional animal care committee. A group of animals each containing five jirds were immunized intraperitoneally with 50 μ g of FEP along with an equal volume of alum (Sigma‐Aldrich) . Control groups were immunized with alum alone.…”

“…The 96‐well microtitre plates (Nunc, Maxisorp; Nalge Nunc International, Denmark) were used, and the wells were coated with FEP (optimum conc. 100 ng/well) prepared in 100 μ l of coating buffer and incubated overnight at 4 °C . After washing and blocking with 5% skim milk solution, a serial twofold dilution of FEP antisera was carried out.…”