Hookworms, a prevalent soil-transmitted helminth (STH), significantly burden approximately 500 to 740 million individuals worldwide, particularly affecting vulnerable populations in low- and middle-income countries (1,2). This study aims to develop a targeted vaccine against hookworm infections by exploiting the proteins present in helminth extracellular vesicles (EVs). These EVs play a crucial role in host-parasite communication and facilitate the worm’s ability to evade immune elimination by suppressing inflammatory responses in the gut(3,4). To exploit this mechanism, the corona and membrane proteomes of isolated EVs derived from the rodent hookworm, Nippostrongylous brasiliensis (Nb), will be characterized using Mass Spectrometry. Abundantly expressed recombinant proteins from the EV surface, will be identified as potential vaccine targets, then expressed in recombinant form using a mammalian cell expression system. The vaccine's effectiveness will be evaluated by inducing antibody responses through mouse vaccinations, followed by challenge experiments using Nb infective stage larvae. Efficacy will be assessed by quantifying worm and egg burdens, and mechanism of vaccine action will be assessed by determining whether antibodies bind to the EV surface and interrupt vesicle uptake by target cells from the mammalian host gut.By identifying potential antigens within the EV corona, this research holds promise for designing an effective vaccine that can alleviate the burden of hookworm infections, especially among vulnerable populations in resource-limited settings.