Open AccessOral Vaccination with AttenuatedSalmonella entericaStrains Encoding T-Cell Epitopes from Tumor Antigen NY-ESO-1 Induces Specific Cytotoxic T-Lymphocyte Responses
Author(s) -
Jia-Zi Meng,
Yi Dong,
He Huang,
Shuang Li,
Yi Zhong,
Shulin Liu,
Yuedan Wang
Publication year - 2010
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cvi.00044-10
Subject(s) - biology , salmonella enterica , epitope , antigen , cytotoxic t cell , microbiology and biotechnology , immune system , salmonella , fimbria , virology , immunology , escherichia coli , gene , bacteria , in vitro , biochemistry , genetics
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 onSalmonella enterica serovar Typhimurium SL3261. The T-cell epitopes (NY-ESO-1 p157-165 and p157-167) from NY-ESO-1, which is a promising target antigen in patients for the specific immune recognition of cancer, were incorporated into the gene encoding AgfA (the major subunit protein of thin aggregative fimbriae ofSalmonella ) by replacing an equal length of the DNA segment. To improve cytotoxic T-lymphocyte recognition, both termini of the peptide were flanked by double alanine (AA) residues. Immunofluorescence microscopy with AgfA-specific antiserum verified the expression of chimeric AgfA, which was also proved by a Congo red binding assay. Oral immunizations of HLA-A*0201 transgenic mice with recombinant SL3261 strains encoding NY-ESO-1 p157-165 or p157-167 induced NY-ESO-1 p157-165-specific CD8+ T cells, detected by an HLA-A*0201 pentamer, and induced a T-cell response detected by an enzyme-linked immunospot assay. TheSalmonella fimbrial display system was efficient at the induction of an antitumor cellular immune responsein vivo , providing a new strategy for the development of efficient cancer vaccinations.