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Biotechnol Lett ; 43(9): 1933-1944, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34313864

RESUMEN

OBJECTIVES: Human papillomavirus infection (HPV) is the most common viral infection which is causes of cervical, penal, vulvar, anal and, oropharyngeal cancer. E7 protein of HPV is a suitable target for induction of T cell responses and controlling HPV-related cancer. The aim of the current study was to designed and evaluated a novel fusion protein containing the different E7 proteins of the HPV 16, 18, 6 and 11, linked to the cell-penetrating peptide HIV-1 Tat 49-57, in order to improve cytotoxic immune responses in in-vitro and in-vivo. RESULTS: In this study whole sequence of HPV16,18,6,11 E7-Tat (47-57) and HPV16,18,6,11 E7 cloned into the vector and expressed in E. coli (BL21). The purified protein was confirmed by SDS page and western blotting and then injected into the C57BL/6 mice. The efficiency of the fusion protein vaccine was assessed by antibody response assay, cytokine assay (IL-4 and IFN-γ), CD + 8 cytotoxicity assay and tumor challenge experiment. Result showed that fusion proteins containing Adjuvant (IFA,CFA) could express higher titer of antibody. Also, we showed that vaccination with E7-Tat and, E7-Tat-ADJ induced high frequencies of E7-specific CD8 + T cells and CD107a expression as well as IFN-γ level and enhanced long-term survival in the therapeutic animal models. CONCLUSION: Our finding suggested that this novel fusion protein vaccine was able to induce therapeutic efficacy and immunogenicity by improving CD8 + T cell in TC-1 tumor bearing mice; so this vaccine may be appreciated for research against HPV and tumor immunotherapies.


Asunto(s)
Alphapapillomavirus/metabolismo , VIH-1/genética , Neoplasias Pulmonares/virología , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Fragmentos de Péptidos/genética , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Alphapapillomavirus/genética , Alphapapillomavirus/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/metabolismo , Clonación Molecular , Escherichia coli/genética , Escherichia coli/crecimiento & desarrollo , Femenino , VIH-1/metabolismo , Papillomavirus Humano 11/genética , Papillomavirus Humano 11/metabolismo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/metabolismo , Papillomavirus Humano 6/genética , Papillomavirus Humano 6/metabolismo , Humanos , Neoplasias Pulmonares/prevención & control , Ratones , Ratones Endogámicos C57BL , Proteínas E7 de Papillomavirus/genética , Vacunas contra Papillomavirus/inmunología , Vacunas contra Papillomavirus/metabolismo , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismo , Vacunación , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/metabolismo
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