Aquaculture is vital to global food security, but the industry is increasingly threatened by bacterial pathogens that cause significant economic losses. Among these, Photobacterium damselae subsp. piscicida is a major pathogen in the Mediterranean area, causing high mortality rates in valuable fish species like the gilthead seabream and Senegalese sole. Traditional vaccination methods in aquaculture often face challenges, including poor efficacy and the stress caused to fish during handling. Thus, there is a critical need for innovative and effective vaccine strategies that are easy to administer and provide robust protection. This proposal (PhotoVaccine) aims to address this challenge by developing novel oral vaccines using spores of probiotic Bacillus strains to deliver Phdp antigens. Building on the NUTRIMU group’s recent proof-of-concept for spore surface display technology, this proposal aims to: i) engineer Bacillus spores to display Phdp antigens on their surface, and ii) assess the immunomodulatory effects and protective efficacy of these PhotoVaccines in fish models. Specifically, we will address the following questions: – Can spores of B. subtilis be used as oral delivery vehicles for Ph. damselae subsp. piscicida antigens? – Are oral PhotoVaccines effective in protecting fish against infections? – What type of response is elicited by oral PhotoVaccines on fish intestinal mucosa? By the end of this project, we aim to develop at least one PhotoVaccine candidate with potential for commercial use, contributing significantly to disease management in aquaculture. This research will also enhance our understanding of fish immunology, particularly how mucosal vaccines can overcome intestinal tolerance to provide longterm protection. The outcomes of this project could transform disease control in aquaculture, promoting sustainability and reducing economic losses due to bacterial infections.