Design, Immune Responses and Anti-Tumor Potential of an HPV16 E6E7 Multi-Epitope Vaccine

Author(s):Show less -

Fernandes de Oliveira, Liliane Maria ^[1] ; Morale, Mirian Galliote ^[1] ; Chaves, Agatha A. Muniz ^[1] ; Cavalher, Aline Marques ^[1] ; Lopes, Aline Soriano ^[2] ; Diniz, Mariana de Oliveira ^[3] ; Schanoski, Alessandra Soares ^[1] ; de Melo, Robson Lopes ^[2] ; de Souza Ferreira, Luis Carlos ^[3] ; de Oliveira, Maria Leonor S. ^[1] ; Demasi, Marilene ^[4] ; Ho, Paulo Lee ^[1]

Affiliation

^[1] Inst Butantan, Lab Biotecnol Mol 1, Sao Paulo, SP - Brazil

^[2] Inst Butantan, Lab Especial Toxinol Aplicada, CeTICS, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508 Sao Paulo, SP - Brazil

^[4] Inst Butantan, Lab Bioquim & Biofis, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 10, n. 9 SEP 21 2015.
• Web of Science Citations: 4

Abstract

Cervical cancer is a common type of cancer among women worldwide and infection with high-risk human papillomavirus (HPVs) types represents the major risk factor for the etiopathogenesis of the disease. HPV-16 is the most frequently identified HPV type in cervical lesions and expression of E6 and E7 oncoproteins is required for the uncontrolled cellular proliferation. In the present study we report the design and experimental testing of a recombinant multi-epitope protein containing immunogenic epitopes of HPV-16 E6 and E7. Tumor preventive assays, based on the engraftment of TC-1 cells in mice, showed that the E6E7 multi-epitope protein induced a full preventive anti-tumor protection in wild-type mice, as well as in mice deficient in expression of CD4(+) T cells and TLR4 receptor. Nonetheless, no anti-tumor protection was observed in mice deficient in CD8(+) T cells. Also, the vaccine promoted high activation of E6/E7-specific T cells and in a therapeutic-approach, E6E7 protein conferred full anti-tumor protection in mice. These results show a potential use of this E6E7 multi-epitope antigen as a new and promising antigen for the development of a therapeutic vaccine against tumors induced by HPV. (AU)

• FAPESP's process: 10/04490-4 - Evaluation of an E6 and E7 multiepitope fused or not to ubiquitin against HPV16 derived cervical cancer
• Grantee: Liliane Maria Fernandes de Oliveira
• Support Opportunities: Scholarships in Brazil - Master