Disorganized muscle protein-1 (DIM-1) of filarial parasite Brugia malayi: cDNA cloning, expression, purification, structural modeling and its potential as vaccine candidate for human filarial infection

Abstract

We have recently identified disorganized muscle protein-1 (DIM-1) in one of the proinflammatory fractions of the human filaria Brugia malayi adult worm. The present study was undertaken to characterize B. malayi DIM-1 (DIM-1bm) and explore its vaccine potential. In this study we cloned and expressed the DIM-1bm gene, investigated its sequence homology with other nematodes, constructed in silico structural model, purified the recombinant DIM-1bm (rDIM-1bm) protein, and studied the effect of immunization with rDIM-1bm on the establishment of B. malayi infection in Mastomys coucha and BALB/c mice. DIM-1bm showed similarity with DIM-1 of Caenorhabditis elegans, Ascaris suum and Loa loa. Structural modeling revealed three immunoglobulin domains in DIM-1bm indicating that it is a member of immunoglobulin superfamily (IgSF). Immunization with rDIM-1bm protected M. coucha as evidenced by significant reduction in microfilarial burden (36-63%) and adult worm establishment (~50%); these effects were relatable to enhanced activity of macrophages, and IFN- and NO responses, and elevated levels of IgG, IgG1, IgG2a and IgG2b. Further, significantly lesser recovery of developing larval stage of the parasite from rDIM-1bm immunized BALB/c mice confirmed that rDIM-1bm has the capability of protecting the host against B. malayi infection. The nucleotide sequence of DIM-1bm showed only 5% homology with human and mouse DIM-1. This is the first report on cloning, expression, sequence homology and purification of rDIM-1bm and its potential to prevent establishment of B. malayi infection. The findings indicate that DIM-1bm may become a potential vaccine candidate for reducing infection rates in human filariasis.