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Expression, Polyubiquitination, and Therapeutic Potential of Recombinant E6E7 from HPV16 Antigens Fused to Ubiquitin

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Autor(es):
Fernandes de Oliveira, Liliane M. ; Morale, Mirian G. ; Chaves, Agtha A. M. ; Demasi, Marilene ; Ho, Paulo L.
Número total de Autores: 5
Tipo de documento: Artigo Científico
Fonte: MOLECULAR BIOTECHNOLOGY; v. 59, n. 1, p. 46-56, JAN 2017.
Citações Web of Science: 0
Resumo

Ubiquitin-proteasome system plays an essential role in the immune response due to its involvement in the antigen generation and presentation to CD8(+) T cells. Hereby, ubiquitin fused to antigens has been explored as an immunotherapeutic strategy that requires the activation of cytotoxic T lymphocytes. Here we propose to apply this ubiquitin fusion approach to a recombinant vaccine against human papillomavirus 16-infected cells. E6E7 multi-epitope antigen was fused genetically at its N- or C-terminal end to ubiquitin and expressed in Escherichia coli as inclusion bodies. The antigens were solubilized using urea and purified by nickel affinity chromatography in denatured condition. Fusion of ubiquitin to E6E7 resulted in marked polyubiquitination in vitro mainly when fused to the E6E7 N-terminal. When tested in a therapeutic scenario, the fusion of ubiquitin to E6E7 reinforced the anti-tumor protection and increased the E6/E7-specific cellular immune responses. Present results encourage the investigation of the adjuvant potential of the ubiquitin fusion to recombinant vaccines requiring CD8(+) T cells. (AU)

Processo FAPESP: 10/04490-4 - Avaliação da vacina E6E7 e E6E7Ub contra o carcinoma cervical provocado pela infecção do HPV16
Beneficiário:Liliane Maria Fernandes de Oliveira
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 07/51698-7 - Desenvolvimento de vacina terapêutica contra HPV16
Beneficiário:Mirian Galliote Morale
Linha de fomento: Bolsas no Brasil - Mestrado