Protein transfer enhances cellular immune responses to DNA vaccination against SARS-CoV.
The current DNA vaccine formulations are not optimal for stimulation of CD8(+) T cells, which are required for clearing virally-infected cells. Here we show that CD8(+) T cell-stimulating activity can be effectively augmented by combining DNA vaccination with protein transfer. C57BL/6 mice were injected intramuscularly with an anti-SARS-CoV DNA vaccine admixed with a lipid-derived conjugate of 4-1BBL, a potential CD8(+) T-cell co-stimulator. The inclusion of the lipidated co-stimulator greatly enhanced cellular immune responses, especially the CTL response, induced by the DNA vaccine. The adjuvant effect of 4-1BBL was lipidation-dependent, indicating that it functions as a cell membrane-anchored co-stimulator. Results of our study suggest, for the first time, that muscle cells may be modified in situ, at the DNA injection site, into APC-like cells to allow direct priming of CD8(+) T cells and thereby improve the efficacy of DNA vaccines.
Kang
Youmin
Y
State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China.
Chen
Aoshuang
A
Wang
Bin
B
Zheng
Guoxing
G
D053330:4-1BB Ligand / Q000008:administration & dosage / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured / Q000276:immunology; D000086462:Coronavirus Nucleocapsid Proteins; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins / Q000276:immunology*; D019308:Palmitic Acid / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000276:immunology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control; D013205:Staphylococcal Protein A / Q000008:administration & dosage / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D053330:4-1BB Ligand; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000086462:Coronavirus Nucleocapsid Proteins; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D019590:Nucleocapsid Proteins; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D019444:Vaccines, DNA; D019308:Palmitic Acid