Vaccination with human papillomavirus-18 E1 protein plus α-galactosyl-ceramide induces CD8+ cytotoxic response and impairs the growth of E1-expressing tumors

• Published in: Vaccine Vol. 37; no. 9; pp. 1219 - 1228
• Main Authors: Amador-Molina, Alfredo, Trejo-Moreno, Cesar, Romero-Rodríguez, Damaris, Sada-Ovalle, Isabel, Pérez-Cárdenas, Enrique, Lamoyi, Edmundo, Moreno, José, Lizano, Marcela
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 21.02.2019; Elsevier Limited
• Subjects: Antigens; CD8 antigen; Ceramide; Cervical cancer; Cross-protection; Cytology; Cytotoxic CD8+ T cells; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA helicase; E1 protein; Ethics; Flow cytometry; Galactosylceramide; Genomes; Human papillomavirus; Immune clearance; Immune response; Immune response (cell-mediated); Immune system; Immunization; Immunology; Infections; Lesions; Lymphocytes; Lymphocytes T; Melanoma; Natural killer cells; NK cells; Peptides; Plasmids; Proteins; Tumors; Vaccination; Vaccines; Viruses; α-galactosylceramide; E1 protein; Cytotoxic CD8+ T cells; Human papillomavirus; NK cells; α-galactosylceramide
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.12.036

•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.