en fish disease fish disease پژوهشي Orginal research papers <em>Yersinia ruckeri</em> (<em>Y. ruckeri</em>)-associated disease remains a problem in fish farming, despite widespread vaccine use. <em>Y. ruckeri</em> is still one of the main causes of economic loss in the aquaculture industry. In this study, we developed outer membrane vesicles (OMV) as a new antigen and compared its efficacy with the classical antigen (whole-cell bacteria). Rainbow trouts were immunized with <em>Y. ruckeri</em>-derived OMVs and formalin-inactivated whole-cell bacteria by immersion route. The fish were then subjected to an intraperitoneal challenge with live bacteria during 2-10 weeks post-immunization. Subsequently, relative percentage of survival (RPS), antibody titer, lysozyme serum activity, lymphocyte percent and kidney pathological signs were evaluated. The OMV morphology was confirmed by electron microscopy. OMV and whole-cell bacteria immunized fish had higher RPS relative to the control group, but whole-cell bacteria resulted in higher RPS than the OMV group. Moreover, in the whole-cell bacteria group antibody titer was higher than the control and OMV groups. Lymphocyte percentage and lysozyme level in the whole-cell bacteria group was increased compared to OMV and control groups. <em>Y. ruckeri</em>&#39;<em>s </em>pathological damage was observed in the control group, while only eosinophilic secretions were identified for both immunized groups. These findings proved the protection of <em>Y. ruckeri</em>-derived OMV against <em>Y. ruckeri</em>, but whole-cell bacteria in the immersion method had a better effect on disease protection. Rainbow trout, Outer membrane vesicles (OMVs), Yersinia ruckeri, Whole-cell bacteria, Immersion. 187 201 http://jifro.ir/browse.php?a_code=A-10-3974-1&slc_lang=en&sid=1 A. Erfanmanesh erfanmanesh@yahoo.com 100319475328460045473 100319475328460045473 No Animal Biological Product Research Group, Academic Center for Education, Culture and Research (ACECR), Tehran Organization, Tehran, Iran. T. Mohajerfar t.mhjr@yahoo.com 100319475328460045474 100319475328460045474 No Animal Biological Product Research Group, Academic Center for Education, Culture and Research (ACECR), Tehran Organization, Tehran, Iran. D. Nikaein dnikaein@ut.ac.ir 100319475328460045475 100319475328460045475 No Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. A. Mokhtari a.mokhtari@ut.ac.ir 100319475328460045476 100319475328460045476 No Animal Biological Product Research Group, Academic Center for Education, Culture and Research (ACECR), Tehran Organization, Tehran, Iran. B. Beikzadeh b.beikzadeh@bio.ui.ac.ir 100319475328460045477 100319475328460045477 Yes Animal Biological Product Research Group, Academic Center for Education, Culture and Research (ACECR), Tehran Organization, Tehran, Iran.