Ligand binding properties of two Brugia malayi fatty acid and retinol (FAR) binding proteins and their vaccine efficacies against challenge infection in gerbils

Zhan, B. et al. (2018) Ligand binding properties of two Brugia malayi fatty acid and retinol (FAR) binding proteins and their vaccine efficacies against challenge infection in gerbils. PLoS Neglected Tropical Diseases, 12(10), e0006772. (doi: 10.1371/journal.pntd.0006772) (PMID:30296268) (PMCID:PMC6193737)

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Parasitic nematodes produce an unusual class of fatty acid and retinol (FAR)-binding proteins that may scavenge host fatty acids and retinoids. Two FARs from Brugia malayi (Bm-FAR-1 and Bm-FAR-2) were expressed as recombinant proteins, and their ligand binding, structural characteristics, and immunogenicities examined. Circular dichroism showed that rBm-FAR-1 and rBm-FAR-2 are similarly rich in α-helix structure. Unexpectedly, however, their lipid binding activities were found to be readily differentiated. Both FARs bound retinol and cis-parinaric acid similarly, but, while rBm-FAR-1 induced a dramatic increase in fluorescence emission and blue shift in peak emission by the fluorophore-tagged fatty acid (dansyl-undecanoic acid), rBm-FAR-2 did not. Recombinant forms of the related proteins from Onchocerca volvulus, rOv-FAR-1 and rOv-FAR-2, were found to be similarly distinguishable. This is the first FAR-2 protein from parasitic nematodes that is being characterized. The relative protein abundance of Bm-FAR-1 was higher than Bm-FAR-2 in the lysates of different developmental stages of B. malayi. Both FAR proteins were targets of strong IgG1, IgG3 and IgE antibody in infected individuals and individuals who were classified as endemic normal or putatively immune. In a B. malayi infection model in gerbils, immunization with rBm-FAR-1 and rBm-FAR-2 formulated in a water-in-oil-emulsion (®Montanide-720) or alum elicited high titers of antigen-specific IgG, but only gerbils immunized with rBm-FAR-1 formulated with the former produced a statistically significant reduction in adult worms (68%) following challenge with B. malayi infective larvae. These results suggest that FAR proteins may play important roles in the survival of filarial nematodes in the host, and represent potential candidates for vaccine development against lymphatic filariasis and related filarial infections.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Kennedy, Professor Malcolm
Creator Roles:
Kennedy, M. W.Data curation, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing
Authors: Zhan, B., Arumugam, S., Kennedy, M. W., Tricoche, N., Lian, L.-Y., Asojo, O. A., Bennuru, S., Bottazzi, M. E., Hotez, P. J., Lustigman, S., and Klei, T. R.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN (Online):1935-2735
Copyright Holders:This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose
First Published:First published in PLoS Neglected Tropical Diseases 12(10): e0006772
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
465741Structural and biophysical analysis of novel lipid binding proteins from parasitic helminthsMalcolm KennedyWellcome Trust (WELLCOTR)083625/Z/07/ZLS - ANIMAL BIOLOGY