Optimization of epicutaneous immunization for the induction of CTL.
The immune system of the skin has recently been exploited for the development of non-invasive vaccine technologies. However, one of the limitations of current vaccine protocols is the inefficient priming of cytotoxic T lymphocytes (CTL). In this study, we report that the application of either an immunodominant class I MHC restricted ovalbumin peptide or whole ovalbumin protein, to tape-stripped skin together with the co-application of the bacterial enterotoxin cholera toxin (CT) induces antigen-specific CTL. Tape-stripping (TS) was found to enhance the magnitude of antibody responses to co-administered protein and to promote the generation of antigen-specific IgG(2a) responses. As well, both cholera toxin and tape-stripping enhanced epidermal dendritic cell (DC) immigration into draining lymph nodes. The adjuvant effect of co-administered cholera toxin and tape-stripping in promoting CTL priming was not dependent on IL-12. Epicutaneous immunization has previously been shown to induce robust antibody responses to administered protein antigen. We now demonstrate the induction of robust and persistent CTL responses to epicutaneously administered protein antigen. Epicutaneous immunization is cheap, simple and effective. These findings suggest the potential use of the skin for the generation of protective immune responses to both viral and tumor challenge.
Kahlon
Roopjeet
R
Department of Medicine, BC Research Institute of Children's and Women's Health, University of British Columbia, Vancouver, BC, Canada.
Hu
Yuxiang
Y
Orteu
Catherine H
CH
Kifayet
Arnawaz
A
Trudeau
Jacqueline D
JD
Tan
Rusung
R
Dutz
Jan P
JP
D000279:Administration, Cutaneous; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D018664:Interleukin-12; D010047:Ovalbumin; D002772:Cholera Toxin