Publications by authors named "Ramanathan Aparnaa"

Human lymphatic filariasis, the parasitic disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori, is ranked as the second most complex clinical condition leading to permanent and long-term disability. The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T and B cell epitopes as the constituents of a single immunogen. Here, we report on the design, chemical synthesis, and immunoprophylaxis of three epitopes that have been identified from promising vaccine candidates reported in our previous studies, constructed as MAP on an inert lysine core for human lymphatic filariasis in Jird model.

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Background: Abundant Larval Transcript (ALT) is one of the major groups of immune-dominant proteins produced by filarial worms during their larval stage. The major B-cell and T-cell epitopic domains of the ALT-2 antigen were mapped to develop a multiple antigenic peptide (MAP) prophylactic antigen against lymphatic filariasis.

Methods And Results: ALT MAP was constructed by solid phase peptide synthesis.

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The chromadorea abundant larval transcript (ALT) family of proteins contains ALT one of the most studied putative vaccine candidate in experimental filariasis. This study reports the characterization of Wuchereria bancrofti 20/22 (Wb20/22) as a member of chromadorea, the ALT family of proteins from the L3 stage of W. bancrofti.

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ALT-2, a novel antigen belonging to the chromadorea ALT-2 family of the filarial nematode is proved to clear filarial parasites in Jirds. In order to increase the protection efficacy by stimulating the cell mediated immunity, MPLA a detoxified derivative of LPS known to induce the cellular response, was used in this study as an adjuvant on mice models. ALT-2+MPLA formulation elicited a high titer of total IgG antibody, with profoundly increased levels of IgG2b.

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Filarial parasites infected nearly 160 million of the global population with onchocerciasis and lymphatic filariasis, and further, a billion of people are estimated to be at risk of infection, rendering them among the most prevalent infectious agents in the world today. Given the complexity of their life cycle and the immune evasion mechanisms of these organisms, development of a vaccine remains to be a long-term challenge. Though a number of immunodominant antigens have been characterized, the presence of homologous proteins in humans or the allelic variants are some of the major drawbacks.

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Filarial thiordoxin peroxidase is a major antioxidant that plays a crucial role in parasite survival. Although Brugia malayi TPx has been shown to be a potential vaccine candidate, it shares 63% homology with its mammalian counterpart, limiting its use as a vaccine or drug target. In silico analysis of TPx sequence revealed a linear B epitope in the host's nonhomologous region.

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