Lymphatic filariasis is a debilitating disease that afflicts over 70 million people worldwide. It is caused by the parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Despite substantial success, efforts to eliminate LF will likely require more time and resources than predicted. Identifying new
drug and
vaccine targets in adult filariae could help elimination efforts. This study's aim was to evaluate intestinal
proteins in adult Brugia malayi worms as possible therapeutic targets. Using
short interfering RNA (
siRNA), we successfully targeted four candidate gene transcripts: Bma-
Serpin, Bma-ShTK, Bma-Reprolysin, and Bma-LAD-2. Of those, Bma-LAD-2, an
immunoglobulin superfamily
cell adhesion molecule (IgSF CAM), was determined to be essential for adult worm survival. We observed a 70.42% knockdown in Bma-LAD-2 transcript levels 1 day post-
siRNA incubation and an 87.02% reduction in
protein expression 2 days post-
siRNA incubation. This inhibition of Bma-LAD-2 expression resulted in an 80% decrease in worm motility over 6 days, a 93.43% reduction in microfilaria release (Mf) by day 6 post-
siRNA incubation, and a dramatic decrease in (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) reduction. Transmission electron microscopy revealed the loss of microvilli and unraveling of mitochondrial cristae in the intestinal epithelium of Bma-LAD-2
siRNA-treated worms. Strikingly, Bma-LAD-2
siRNA-treated worms exhibited an almost complete loss of pseudocoelomic fluid. A
luciferase immunoprecipitation system assay did not detect anti-Bma-LAD-2
IgE in the serum of 30 LF patients, indicating that LF exposure does not result in
IgE sensitization to this
antigen. These results indicate that Bma-LAD-2 is an essential
protein for adult Brugia malayi and may be an effective therapeutic target. IMPORTANCE Brugia malayi is a parasitic nematode that can cause
lymphatic filariasis, a debilitating disease prevalent in tropical and subtropical countries. Significant progress has been made toward eliminating the disease. However, complete eradication may require new
therapeutics such as drugs or a
vaccine that kill adult filariae. In this study, we identified an
immunoglobulin superfamily
cell adhesion molecule (Bma-LAD-2) as a potential
drug and
vaccine candidate. When we knocked down Bma-LAD-2 expression, we observed a decrease in worm motility, fecundity, and metabolism. We also visualized the loss of microvilli, destruction of the mitochondria in the intestinal epithelium, and loss of pseudocoelomic fluid contents after Bma-LAD-2
siRNA treatment. Finally, we demonstrated that serum from filaria-infected patients does not contain preexisting
IgE to Bma-LAD-2, which indicates that this
antigen would be safe to administer as a
vaccine in populations where the disease is endemic.