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A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins
Heidar Ali Panahi1, Azam Bolhassani2, Gholamreza Javadi1
1Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
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.
Insights
This study identifies potential CD8+ T cell epitopes from Human Papillomaviruses (HPVs) oncoproteins to aid in developing effective therapeutic vaccines against HPV-associated cancers.
Area of Science:
- * Virology and Immunology
- * Cancer Research and Therapeutics
Background:
- * Human papillomaviruses (HPVs), particularly HPV16 and 18, are major causes of epithelial cell malignancies, contributing to a significant global cancer burden.
- * Developing effective therapeutic vaccines against HPV-associated cancers requires identifying tumor-associated epitopes that elicit strong cell-mediated immune responses.
- * Early viral oncoproteins (E5, E6, E7) are crucial for cancer induction and maintenance, making them targets for epitope prediction.
Purpose of the Study:
- * To predict and identify potential CD8+ T cell epitopes from HPV16, 18, 31, and 45 oncoproteins.
- * To provide a rational basis for developing DNA- or peptide-based therapeutic vaccines against HPV-driven cancers.
- * To identify candidate epitopes for preclinical vaccine studies.
Main Methods:
- * A two-step computational approach was employed to predict T cell epitopes.
- * Analyses included MHC class I and II binding, processing, population coverage, immunogenicity, protein-peptide docking, epitope conservation, and cross-reactivity with host antigens.
- * Multiple bioinformatics tools were utilized to assess epitope candidates.
Main Results:
- * The study successfully predicted five probable CD8+ T cell epitopes for each targeted HPV oncoprotein, totaling 60 epitopes.
- * These epitopes demonstrated favorable scores through an integrated prediction approach.
- * The identified epitopes are considered valuable candidates for further therapeutic vaccine research.
Conclusions:
- * The predicted HPV epitopes serve as promising candidates for in vitro and in vivo therapeutic vaccine studies against HPV-associated cancers.
- * The established two-step prediction strategy offers a robust framework for future vaccine development against viral oncogenesis.
- * This research contributes to the ongoing efforts to combat the significant health challenge posed by HPV-related malignancies.
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