Salmonella expressing a T-cell epitope from Sendai virus are able to induce anti-infection immunity

Abstract

Bacterial fimbriae can accept foreign peptides and display them on the cell surface. A highly efficient gene replacement method was used to generate peptide vaccines based on Salmonella enterica subsp. enterica serovar Typhimurium LT2. DNA encoding an epitope from Sendai virus, SV9 (Sendai virus nucleoprotein peptide 324–332, FAPGNYPAL), which is known to induce cytotoxic T lymphocytes, was incorporated into the gene encoding AgfA (the major subunit protein of thin aggregative fimbriae of Salmonella) by replacing an equal length DNA segment. To improve cytotoxic T lymphocyte recognition, both termini of the peptide were flanked by double alanine (AA) or arginine (RR) residues. Western blotting and immunofluorescence microscopy using AgfA-specific antiserum verified the expression of chimeric AgfA; expression was also proved by a Congo red binding assay. Oral immunizations of C57BL/6 mice with the four strains induced an epitope-specific T-cell response (detected by enzyme-linked immunosorbent spot assay). When the mice were challenged with the Sendai virus, the magnitude of the infection was significantly reduced in the immunized groups compared with the controls. The Salmonella fimbrial display system efficiently induces a cellular immune response and anti-infection immunity in vivo, providing a new strategy for the development of efficient peptide vaccination.

Secretion and functional display of fusion proteins through the curli biogenesis pathway

“…In previous studies, short peptide stretches (9 to 16 residues in length) within the major Salmonella curli subunit, AgfA, have been successfully replaced by different T‐cell epitopes (White et al ., 1999; 2000; Huang et al ., ; Meng et al ., ). To further explore whether there are sequence specific or structural restrictions for passage through the CsgG transmembrane pore, a more extensive heterologous sequence was fused to the CsgA C‐terminus.…”

Balancing Innate Immunity and Inflammatory State via Modulation of Neutrophil Function: A Novel Strategy to Fight Sepsis

“…Neutralization of LPS using antibodies reduced the LPS induced inflammatory response [ 32 ]. Currently, vaccination strategies to increase the elimination of pathogens are under investigation [ 34 ]. None of these antiendotoxin strategies reached wide clinical acceptance.…”

Oral Vaccination with AttenuatedSalmonella entericaStrains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses

“…It has been clearly established that the use of attenuated Salmonella strains as live oral vaccines is a safe and effective means of inducing significant humoral and secretory antibody responses in animal species, including humans and mice (8,16,21,(32)(33)(34). The use of plasmid-based expression systems to elevate foreign antigen levels in Salmonella live vaccine vectors is ideal, but these systems have the serious disadvantages of instability and selective requirements in vivo (10,14,17,38).…”