A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

Abstract

Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues. A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide. Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them. Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response. Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers. Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study. For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes. In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools. Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach. These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers. Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development.

Development of HPV16,18,31,45 E5 and E7 peptides-based vaccines predicted by immunoinformatics tools

“…In this study, we considered E5 protein as a novel target and E7 protein as a major target in vaccine design. Based on our previous study (Panahi et al 2018) and to overcome the MHC limitation, the long overlapping peptide constructs containing HPV 16,18,31,45 E5 and E7 epitopes were designed. These epitopes had the highest scores in important parameters such as binding affinity between peptide and MHC, MHC-I processing, peptide-MHC docking and population coverage.…”

“…Based on our previous study (Panahi et al 2018), eight epitopes for both E5 (SAFRCFIVYIIFVYIPL-FLIHTHARF-HPV16, SPATAFTVYVFCFLL-HPV18, YVVFIYIPLFVIHTHASF-HPV31, QSVYV-CAFAWLLVF-HPV45) and E7 (GQAEPDRAHY-NIVTF-HPV16, SSADDLRAFQQLFL-HPV18, GQAEPDTSNYNIVTF-HPV31 and TLQEIVLH-LEPQNELDPVDLL-HPV45) proteins were selected. According to bioinformatics analysis, these epitopes had the highest scores in important parameters such as binding affinity between peptide and MHC, MHC-I processing, peptide-MHC docking, and population coverage.…”

“…Based on our previous study (Panahi et al 2018), two different peptide constructs were designed (Fig. 1).…”

Verificação Da Temperatura De Distribuição De Refeições Quentes Ofertadas Em Uma Instituição De Longa Permanência Para Idosos E a Correlação Com O Crescimento Microbiológico

“…los como vacinas peptídicas, as quais vêm apresentando resultados interessantes e promissores em determinados vírus (ADHIKARI; TAYEB;RAHMAN, 2018; CASTELLI et a.l, 2013;LI et al, 2014;YASMIN;NABI, 2016) .Vacinas que utilizam proteínas recombinantes já são aplicadas a projetos que estudam aplicação e desenvolvimento vacinais contra determinados vírus como o HVB e o HPV (NACIMENTO;LEITE, 2012;PANAHI et al, 2018) . Atualmente vários trabalhos são realizados trazendo a predição in silico e análises de bioinformática para epítopos que podem ser utilizados em projetos de possíveis vacinas que sejam eficientes.…”

Staphylococcus aureus: UMA VISÃO GERAL DOS MECANISMOS DE VIRULÊNCIA E RESISTÊNCIA

“…Avaliação da semi vida de cada proteína pelo ProtParam tool. los como vacinas peptídicas, as quais vêm apresentando resultados interessantes e promissores em determinados vírus (ADHIKARI; TAYEB;RAHMAN, 2018; CASTELLI et a.l, 2013; LI et al, 2014;YASMIN;NABI, 2016) .Vacinas que utilizam proteínas recombinantes já são aplicadas a projetos que estudam aplicação e desenvolvimento vacinais contra determinados vírus como o HVB e o HPV (NACIMENTO; LEITE,PANAHI et al, 2018) . Atualmente vários trabalhos são realizados trazendo a predição in silico e análises de bioinformática para epítopos que podem ser utilizados em projetos de possíveis vacinas que sejam eficientes.…”