Mutant FAR protein construction and their potential as vaccine candidates

Abstract

Fatty acid and retinol binding proteins are a family of proteins found in free living and parasitic nematodes. It is our hypothesis that parasitic nematodes secrete FAR into host tissues, resulting in localized immunosuppression, and hence chronic parsitic infection. Heligmosomoides polygyrus is a mouse model for hookworm that is commonly used in the laboratory for the investigation of the cellular responses to chronic helminth infections. Our laboratory is investigating a protein retrieved from the L4 larval stage of this parasite, a protein believed to be involved in assisting the parasite to form and maintain chronic infections. We have termed this protein Hp‐FAR‐1, for H. polygyrus Fatty Acid and Retinol Binding Protein 1. Creation of mutant FAR proteins that do not bind retinol are of interest for the development of potential vaccine candidates. The purpose of this study was to compare Ce‐FAR‐4, a non‐functional FAR protein from C. elegans, with parasitic FAR proteins. The primary amino acid structures of both parasitic and Ce‐FAR‐4 were analyzed for regions of conservation. Specifically, we target regions that were conserved among the parasitic proteins, including Hp‐FAR‐1, but not in Ce‐FAR‐4; hypothesizing that mutating the conserved regions of Hp‐FAR‐1to the amino acids found in Ce‐FAR‐4 would inhibit retinol binding.