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However, their efficacy is limited by low immunogenicity and gastrointestinal degradation after oral administration. To address this issue, low\u2010endotoxin\n                    <jats:italic>Salmonella choleraesuis<\/jats:italic>\n                    strain SC\u2010L3 was engineered via lipid A modification to generate bacterial biomimetic vesicles (BBVs) with reduced endotoxin activity. BBVs were functionalized using ClyA\u2010embedded SpyCatcher and Streptococcus protein G for dual antigen coupling, and further coated with chitosan oligosaccharides (COS) to enhance mucosal penetration and gastrointestinal stability. Using mCherry as a model antigen, we obtained optimized mCherry\u2010CSS\u2010BBV@COS that showed high antigen protection rates (83% and 63% in simulated gastric and intestinal fluids, respectively), capacity for lysosomal escape and effective stimulation of M1 macrophage polarization in vitro. Oral administration of mCherry\u2010CSS\u2010BBV@COS elicited robust systemic IgG and mucosal sIgA responses in mice. Furthermore, dual\u2010antigen BBV conjugates (GDH\u2010gD\u2010Fc\u2010CSS\u2010BBV@COS) co\u2010delivering\n                    <jats:italic>Streptococcus suis<\/jats:italic>\n                    glutamate dehydrogenase and pseudorabies virus gD\u2010Fc induced antigen\u2010specific humoral, mucosal and cellular immunity, conferring complete protection against lethal challenges with the respective pathogens. In summary, we generated a versatile, low\u2010endotoxin BBV platform for oral combination subunit vaccines, offering a novel strategy for protection against viral and bacterial infections.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70207","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T12:21:34Z","timestamp":1764418894000},"source":"Crossref","is-referenced-by-count":6,"title":["Engineered Low\u2010Endotoxin Bacterial Biomimetic Vesicles for Enhanced Oral Dual\u2010Antigen Subunit Vaccine Delivery"],"prefix":"10.1002","volume":"14","author":[{"given":"Xuegang","family":"Shen","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences  Harbin 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