Identification and characterization of nematode specific protective epitopes of Brugia malayi TRX towards development of synthetic vaccine construct for lymphatic filariasis

Madhumathi, Jayaprakasam; Prince, Prabhu Rajaiah; Anugraha, Gandhirajan; Pote, Kiran; Rao, D. N.; Reddy, M. Janga; Kaliraj, Perumal

doi:10.1016/j.vaccine.2010.05.012

Cited by 35 publications

(43 citation statements)

References 57 publications

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“…Apart from the homologous sequence, the immuno-modulatory effect of TRX reported by Kunchithapautham et al (2003) sets another limitation for TRX to be used as a vaccine candidate. Hence, epitopic portions which were non homologous to the host proteins (Madhumathi et al, 2010) and were highly reactive to the sera of putatively immune individuals (Endemic normal) were chosen to be constructed as Multi Antigen Peptides on an inert lysine core. The present study which focuses on the immune responses of TT MAP formulated with MDP is an attempt to improve the vaccine effi cacy of TT MAP.…”

Section: Discussionmentioning

confidence: 99%

“…The three peptides were chosen to be synthesised as MAP based on previous studies in mice models (Madhumathi et al, 2010) with individual peptides (Data not shown). All the 3 peptides are bonded to the inert lysine core.…”

Section: Synthesis Of Tt Mapmentioning

confidence: 99%

“…These strategies have facilitated the identifi cation of several potential vaccine candidates offering varying degrees of protection against fi larial infection in animal models (Thirugnanam et al, 2007;Anand et al, 2008;Vanam et al, 2009;Dakshinamoorthy et al, 2013). Antioxidant enzymes thioredoxin (TRX), thioredoxin peroxidase (TPX), glutathione-S-transferase (GST), superoxide dismutase (SOD) and glutathione peroxidase (GPX), most of which are present in all stages of the parasite and have been involved to protect the parasites from the host are reported as promising vaccine candidates (Maizels et al, 2001;Veerapathran et al, 2009;Madhumathi et al, 2010). A new approach in vaccine technology is using recombinant protein subunits as peptide vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…Synthetic peptide vaccines and B-T cell chimera's containing immunodominant regions from antigens have been developed for malaria (Nardin et al, 2001), Schistosomiasis (Arnon et al, 2000) and many other viral and parasitic diseases. Thioredoxin and transglutaminase, though being reported as promising vaccine candidates cannot be used as whole antigen due to the homology that it shares with host proteins (Kunchithapautham et al, 2003;Vanam et al, 2009;Madhumathi et al, 2010). Hence immunologically dominant B and T epitopes from these proteins were identifi ed and constructed as Multi antigen peptide on an inert lysine core.…”

Section: Introductionmentioning

confidence: 99%

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Effect of muramyl dipeptide and alum adjuvants on immunization with Filarial multi antigen peptide vaccine in mice model

et al. 2016

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SummaryFilarial thioredoxin and transglutaminase are enzymes that are secreted throughout the lifecycle of the parasites which are mandatory for the survival of the parasite. They are reported to be promising vaccine candidates, yet the limitation factors of these proteins to be developed as vaccines is their homology they share with the host proteins. Hence immunodominant epitopes from these proteins were constructed as peptides and immunised in mice model with Muramyl dipeptide (MDP) as adjuvant. Immunodominant epitopic portions from Filarial thioredoxin and transglutaminase which are non-homologous with host proteins were constructed as Multi Antigen Peptide (MAP) and assembled in an inert lysine core. The synthesised MAP was immunised with MDP as adjuvant in Balb/c mice model, humoral and cellular immune response were studied. Antibody titre levels for TT MAP with MDP was in par with alum as adjuvant in mice models. T cell responses of TT MAP with MDP showed a balanced T H 1/T H 2 response. The T H 1 cytokines namely IL-2 and IFN-ɤ were also higher in TT MAP immunised groups with MDP as adjuvant whereas alum immunised groups was T H 2 biased. TT MAP admixed with MDP as adjuvant proves to be safe in mice model. Further vaccination studies are underway in permissive animal models to determine the role of TT MAP with MDP as adjuvant in protective immunity against W. bancrofti and B. malayi infections.

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Section: Discussionmentioning

confidence: 99%

Section: Synthesis Of Tt Mapmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effect of muramyl dipeptide and alum adjuvants on immunization with Filarial multi antigen peptide vaccine in mice model

et al. 2016

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“…Hence, in the current study, B. malayi thioredoxin (BmTRX) and Venom Allergen Homologue (BmVAH), two potent filarial vaccine candidates were chosen to make a fusion protein construct designated as TV. Both are expressed predominantly in L3 infective stage and showed high protective efficacy in previous studies (Madhumathi et al 2010, Anand et al 2011. It has been proposed that L3 or infective larvae stage genes are attractive vaccine candidates that will establish the infection in the host (Gomez-Escobar et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Immune responses of B. malayi thioredoxin (TRX) and venom allergen homologue (VAH) chimeric multiple antigen for lymphatic filariasis

Anugraha

Jeyaprita

Madhumathi

et al. 2013

Acta Parasitologica

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Although multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.

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A continuous peptide epitope reacting with pandemic influenza AH1N1 predicted by bioinformatic approaches

et al. 2015

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Computational identification of potential epitopes with an immunogenic capacity challenges immunological research. Several methods show considerable success, and together with experimental studies, the efficiency of the algorithms to identify potential peptides with biological activity has improved. Herein, an epitope was designed by combining bioinformatics, docking, and molecular dynamics simulations. The hemagglutinin protein of the H1N1 influenza pandemic strain served as a template, owing to the interest of obtaining a scheme of immunization. Afterward, we performed enzyme-linked immunosorbent assay (ELISA) using the epitope to analyze if any antibodies in human sera before and after the influenza outbreak in 2009 recognize this peptide. Also, a plaque reduction neutralization test induced by virus-neutralizing antibodies and the IgG determination showed the biological activity of this computationally designed peptide. The results of the ELISAs demonstrated that the serum of both prepandemic and pandemic recognized the epitope. Moreover, the plaque reduction neutralization test evidenced the capacity of the designed peptide to neutralize influenza virus in Madin-Darby canine cells.

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Identification and characterization of nematode specific protective epitopes of Brugia malayi TRX towards development of synthetic vaccine construct for lymphatic filariasis

Cited by 35 publications

References 57 publications

Effect of muramyl dipeptide and alum adjuvants on immunization with Filarial multi antigen peptide vaccine in mice model

Effect of muramyl dipeptide and alum adjuvants on immunization with Filarial multi antigen peptide vaccine in mice model

Immune responses of B. malayi thioredoxin (TRX) and venom allergen homologue (VAH) chimeric multiple antigen for lymphatic filariasis

A continuous peptide epitope reacting with pandemic influenza AH1N1 predicted by bioinformatic approaches

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