Development of a DC-targeting Salmonella- amplifying RNA vector platform co-delivering dual antigens and adjuvants for enhanced protection against H9N2 avian influenza

作者：Wang M, Gao Y, Zhang Y, Yang T, Zhang Y, Sun Y, Guo Q, Zhang G, Gong J, Wang Z, Wang C, Jiang Y · 发表于：Veterinary microbiology · 年份：2026 · DOI：10.1016/j.vetmic.2026.111042 · 研究领域：Influenza A Virus, H9N2 Subtype、Influenza in Birds、Dendritic Cells、Salmonella、Influenza Vaccines、Antigens, Viral、Animals、Chickens、Adjuvants, Immunologic、Neuraminidase、Antibodies, Viral、Genetic Vectors

Avian influenza virus primarily invades the respiratory mucosa, necessitating the establishment of a robust mucosal secretory IgA (sIgA) barrier. However, the efficacy of avian mucosal vaccines is often hindered by inefficient antigen uptake and immune tolerance. Consequently, modern vaccine strategies focus on active targeting delivery, immune microenvironment remodeling, and activation of multifaceted immune responses. The immunogenicity and molecular mechanisms of a novel Salmonella-delivered self-amplifying RNA (saRNA) vector platform were evaluated in this study. This platform integrates bacterial surface display of a dendritic cell (DC)-targeting nanobody (Nb-phage54 via LppOmpA) with co-expression of molecular adjuvants against H9N2 influenza. The expression of HA1 and NA antigens from recombinant plasmids (pYL673, pYL679, and pYL681) was confirmed using confocal microscopy and Western blot analysis. In vitro assays revealed that the Nb-mediated targeting strain (S673) significantly increased invasion efficiency into bone marrow-derived dendritic cells and up-regulated the transcription of CCL5, CCR7, CD83, and CD86, effectively promoting DC maturation. Transcriptomic analysis (RNA-seq) revealed divergent mechanisms among vaccine candidates. The non-targeting group (S615) primarily activated antiviral innate pathways, such as JAK-STAT, whereas the targeting group (S673) significantly improved antigen processing, presentation, and natural killer cell-mediated cytotoxici...