Vaccination with human papillomavirus-18 E1 protein plus α-galactosyl-ceramide induces CD8+ cytotoxic response and impairs the growth of E1-expressing tumors
•Vaccination with E1202-654 + α-GalCer protects against B16-F0/E1244-550 tumor challenge in a prophylactic approach.•E1202-654 + α-GalCer inhibits the growth of established B16-F0/E1244-550 tumors.•The inoculation of α-GalCer elicits a cytotoxic NK cell response.•The immune response mediated by E1-s...
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Veröffentlicht in: | Vaccine 2019-02, Vol.37 (9), p.1219-1228 |
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Sprache: | eng |
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Zusammenfassung: | •Vaccination with E1202-654 + α-GalCer protects against B16-F0/E1244-550 tumor challenge in a prophylactic approach.•E1202-654 + α-GalCer inhibits the growth of established B16-F0/E1244-550 tumors.•The inoculation of α-GalCer elicits a cytotoxic NK cell response.•The immune response mediated by E1-specific CD8+ T cells and NK cells, is involved in the anti-tumor effect.
CD8+ T cell-mediated immune response plays a major role in the clearance of virus-infected cells, including human papillomavirus (HPV). The effective treatment of women with normal cytology but persistent high risk-HPV infection or with low-grade intraepithelial lesions could take advantage of novel strategies based on vaccination with viral immunological targets with a wide spectrum of cross-protection. The helicase E1, expressed early during viral replication in HPV infection, is among the most conserved papillomavirus proteins, which makes it a good vaccine candidate. In the present study, we examined E1-specific CD8+ T cell and NK immune responses in a mouse model with α-galactosylceramide (α-GalCer) as an adjuvant. We found that mice immunized with E1 combined with α-GalCer elicited an E1-specific CD8+ T and NK cell cytotoxic responses, which correlated with growth inhibition of grafted melanoma B16-F0 cells expressing E1, both in prophylactic and therapeutic protocols. |
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ISSN: | 0264-410X 1873-2518 |
DOI: | 10.1016/j.vaccine.2018.12.036 |