Transgenic Schizochytrium as a Promising Oral Vaccine Carrier: Potential Application in the Aquaculture Industry

<i>Schizochytrium limacinum</i> SR21, a kind of eukaryotic heterotrophic organism rich in unsaturated fatty acids, is an emerging microbial alternative to fish oil. The dietary inclusion of 15% SR21 was optimal for the growth performance of zebrafish. Previous studies demonstrated that fructose-1,6-bisphosphate aldolase (FBA) of <i>Edwardsiella tarda</i> is a valuable broad-spectrum antigen against various pathogens in aquaculture (e.g., <i>Aeromonas hydrophila</i>, <i>Vibro anguillarum</i>, <i>Vibro harveyi</i>, <i>Vibro alginolyticus</i>). We pioneered the development of stable <i>S. limacinum</i> SR21 transformants expressing the antigen protein FBA, exploring their potential as a novel oral vaccine for the aquaculture industry. The model animal zebrafish (<i>Danio rerio</i>) and ornamental fish koi carp (<i>Cyprinus carpio</i> koi) were harnessed to assess the immunoprotective effect, respectively. According to the quantitative expression analysis, zebrafish fed with recombinant <i>Schizochytrium</i> expressing FBA exhibited specific immune responses in the intestine. The expression levels of <i>MHC-I</i> and <i>MHC-II</i>, involved in cell-mediated adaptive immune responses, were significantly upregulated on the 14th and 28th days post-immunization. Additionally, the expression of highly specialized antibody genes <i>IgZ1</i> and <i>IgZ2</i> in mucosal immunity were significantly triggered on the 14th day post-immunization. Feeding koi carp with recombinant <i>S. limacinum</i> SR21-FBA increased the production of myeloperoxidase and FBA-specific antibodies in the sera. Furthermore, the sera of koi fed with recombinant <i>S. limacinum</i> SR21-FBA exhibited significant bactericidal activities against pathogen <i>E. tarda</i>. Thus, <i>S. limacinum</i> SR21 is a natural and highly promising oral vaccine carrier that not only provides essential nutrients as a functional feed ingredient but also offers specific immune protection to aquatic animals. This dual application is vital for promoting the sustainable development of the aquaculture industry.