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Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis

Published online by Cambridge University Press:  19 February 2016

J. Madhumathi ,
P.R. Prince ,
D.N. Rao ,
A.A. Karande ,
M.V.R. Reddy  and
P. Kaliraj
J. Madhumathi
Affiliation:
Department of Biotechnology, Indian Institute of Technology, Chennai-600036, India
P.R. Prince
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
D.N. Rao
Affiliation:
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi110029, India
A.A. Karande
Affiliation:
Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram442102, India
M.V.R. Reddy
Affiliation:
Department of Biochemistry, Indian Institute of Science, Bangalore560012, India
P. Kaliraj*
Affiliation:
Centre for Biotechnology, Anna University, Chennai600025, India
*
*Fax: +91 44 22352642 E-mail: pk.kaliraj@gmail.com
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Abstract

Human lymphatic filariasis is a neglected tropical disease, causing permanent and long-term disability with severe immunopathology. Abundant larval transcript (ALT) plays a crucial role in parasite establishment in the host, due to its multi-faceted ability in host immune regulation. Although ALT protein is a key filarial target, its exact function is yet to be explored. Here, we report epitope mapping and a structural model of Brugia malayi ALT-2, leading to development of a multi-epitope vaccine. Structural analysis revealed that ALT represents unique parasitic defence proteins belonging to a toxin family that carries a ‘knottin’ fold. ALT-2 has been a favourite vaccine antigen and was protective in filarial models. Due to the immunological significance of ALT-2, we mapped B-cell epitopes systematically and identified two epitope clusters, 1–30 and 89–128. To explore the prophylactic potential of epitope clusters, a recombinant multi-epitopic gene comprising the epitopic domains was engineered and the protective efficacy of recombinant ALT epitope protein (AEP) was tested in the permissive model, Mastomys coucha. AEP elicited potent antibody responses with predominant IgG1 isotype and conferred significantly high protection (74.59%) compared to ALT-2 (61.95%). This proved that these epitopic domains are responsible for the protective efficacy of ALT-2 and engineering protective epitopes as a multi-epitope protein may be a novel vaccine strategy for complex parasitic infections.

Type
Research Papers
Information
Journal of Helminthology , Volume 91 , Issue 1 , January 2017 , pp. 43 - 54
Copyright
Copyright © Cambridge University Press 2016 

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