Enhanced protective efficacy of a dendritic cell-targeting truncated F protein delivery via minicircle DNA vaccine against genotype VII newcastle disease virus in chickens.

Abstract

Newcastle disease (ND), caused by the Newcastle disease virus (NDV), poses a severe threat to global poultry farming, leading to significant losses annually. The limitations of current ND vaccines in terms of efficacy and duration of protection have encouraged the exploration of novel vaccine designs. This study aimed to adopt a delayed-lysis Salmonella strain χ11218 as vaccine delivery vector. By expressing a truncated NDV fusion (F) protein (tF) fused with a dendritic cell-targeting peptide (DCpep), it was used to enhance immune responses against ND. This study builds on our previous work with the pYL58 plasmid which contained the full-length F protein. We successfully replaced the F protein in the pYL58 with a fusion of DCpep and a tF protein lacking a transmembrane (TM) domain and an intracellular (CT), yielding the recombinant plasmid pYL220. Salmonella χ11218(pYL220) (S220) enhanced the immune response by fusing DCpep with the antigen and modifying the antigen sequence. Compared to vaccination with the parental strain pYL58, immunization using S220 resulted in markedly higher levels of serum IgG and increased levels of sIgA in the lung and intestinal mucosa. For the S220 group, qRT-PCR was used to measure the surface molecules associated with dendritic cell activation and maturation, specifically CCL5, CCR7, CD83, and CD86, in the cultured spleen cell suspension stimulated with 40 µg/mL of F protein for 72 h. Compared to other experimental groups, these molecules were significantly upregulated in the S220 group. Additionally, viral shedding in the lung tissue was significantly reduced in the S220 group compared to other experimental groups and was comparable to that of the vaccine group. Furthermore, the post-challenge survival rates of chicks indicated that S220 provided protection, with rates consistently reaching 50 %. This study indicated that the fusion expression of the truncated antigen and DCpep not only provided immunogenicity but also significantly enhanced the immunological effect due to its easier release from host cells and enhanced targeting of dendritic cells. These findings prove that using Salmonella as a vector to express the tF protein fused with DCpep is feasible, laying the foundation for the development of effective and oral immunized NDV vaccines.