A Lactobacillus plantarum vaccine candidate with dendritic cell targeting and lysosome escape properities provides efficient protection against necrotic enteritis in broiler chickens

作者：Gao Y, Wang M, Wang Y, Zhang Y, Guo Q, Yang T, Sun Y, Zhang Y, Wen X, Lu X, Xu Y, Wang T, Du L, Huang H, Wang Z, Wang C, Jiang Y · 发表于：Veterinary microbiology · 年份：2026 · DOI：10.1016/j.vetmic.2026.111130 · 研究领域：Poultry Diseases、Bacterial Vaccines、Enteritis、Dendritic Cells、Clostridium Infections、Lactiplantibacillus plantarum、Animals、Chickens、Clostridium perfringens、Lysosomes、Antibodies, Bacterial、Protein Subunit Vaccines

Necrotic enteritis (NE) caused by Clostridium perfringens (C.perfringen) type G strains remains a critical threat to the global poultry industry, particularly with the restricted use of antibiotics. The core virulence factor Necrotic Enteritis B-like Toxin (NetB), along with the adhesion factors Fimbrial protein A (FimA) and Fructose-1,6-bisphosphate aldolase (Fba), are key targets for multivalent vaccination. In this study, we developed a surface-displayed Lactobacillus plantarum (L. plantarum) NC8 vaccine, NC8(pYL590), which co-expressed NetB, FimA, and Fba on the bacterial surface. To overcome the disadvantages associated with traditional mucosal vaccines, we integrated a dendritic cell (DC) targeting nanobody (phi54) and a lysosome-escape peptide (Pas). In vitro study showed that phi54-mediated targeting significantly enhanced DC capture efficiency and induced metabolic reprogramming, specifically characterized by the upregulation of ribosomal and oxidative phosphorylation pathways in NC8(pYL590) group. Furthermore, the Pas peptide facilitated lysosomal escape, promoting antigen cross-presentation. Consequently, oral immunization with NC8(pYL590) elicited systemic IgY and mucosal secretory IgA (sIgA) responses and induced a Th1/Th2 cellular immunity, as evidenced by elevated IFN-γ and IL-4 levels. In the challenge model, NC8(pYL590) conferred partial effective protection, reduced the intestinal average lesion score to 1.0 (compared to 3.25 in the PBS group) and prevented ...