Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza
Abstract When it was first introduced in 2000, reverse vaccinology was defined as an in silico approach that begins with the pathogen's genomic sequence. It concludes with a list of potential proteins with a possible, but not necessarily, list of peptide candidates that need to be experimentall...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12859-023-05374-1 |
| _version_ | 1797806517276114944 |
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| author | Giulia Russo Elena Crispino Avisa Maleki Valentina Di Salvatore Filippo Stanco Francesco Pappalardo |
| author_facet | Giulia Russo Elena Crispino Avisa Maleki Valentina Di Salvatore Filippo Stanco Francesco Pappalardo |
| author_sort | Giulia Russo |
| collection | DOAJ |
| description | Abstract When it was first introduced in 2000, reverse vaccinology was defined as an in silico approach that begins with the pathogen's genomic sequence. It concludes with a list of potential proteins with a possible, but not necessarily, list of peptide candidates that need to be experimentally confirmed for vaccine production. During the subsequent years, reverse vaccinology has dramatically changed: now it consists of a large number of bioinformatics tools and processes, namely subtractive proteomics, computational vaccinology, immunoinformatics, and in silico related procedures. However, the state of the art of reverse vaccinology still misses the ability to predict the efficacy of the proposed vaccine formulation. Here, we describe how to fill the gap by introducing an advanced immune system simulator that tests the efficacy of a vaccine formulation against the disease for which it has been designed. As a working example, we entirely apply this advanced reverse vaccinology approach to design and predict the efficacy of a potential vaccine formulation against influenza H5N1. Climate change and melting glaciers are critical due to reactivating frozen viruses and emerging new pandemics. H5N1 is one of the potential strains present in icy lakes that can raise a pandemic. Investigating structural antigen protein is the most profitable therapeutic pipeline to generate an effective vaccine against H5N1. In particular, we designed a multi-epitope vaccine based on predicted epitopes of hemagglutinin and neuraminidase proteins that potentially trigger B-cells, CD4, and CD8 T-cell immune responses. Antigenicity and toxicity of all predicted CTL, Helper T-lymphocytes, and B-cells epitopes were evaluated, and both antigenic and non-allergenic epitopes were selected. From the perspective of advanced reverse vaccinology, the Universal Immune System Simulator, an in silico trial computational framework, was applied to estimate vaccine efficacy using a cohort of 100 digital patients. |
| first_indexed | 2024-03-13T06:08:32Z |
| format | Article |
| id | doaj.art-7ff803bd435f487487fae84ec60b93ad |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-03-13T06:08:32Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-7ff803bd435f487487fae84ec60b93ad2023-06-11T11:26:57ZengBMCBMC Bioinformatics1471-21052023-06-0124112210.1186/s12859-023-05374-1Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenzaGiulia Russo0Elena Crispino1Avisa Maleki2Valentina Di Salvatore3Filippo Stanco4Francesco Pappalardo5Department of Health and Drug Sciences, Università degli Studi di CataniaDepartment of Biomedical and Biotechnological Sciences, Università degli Studi di CataniaDepartment of Mathematics and Computer Science, Università degli Studi di CataniaDepartment of Health and Drug Sciences, Università degli Studi di CataniaDepartment of Mathematics and Computer Science, Università degli Studi di CataniaDepartment of Health and Drug Sciences, Università degli Studi di CataniaAbstract When it was first introduced in 2000, reverse vaccinology was defined as an in silico approach that begins with the pathogen's genomic sequence. It concludes with a list of potential proteins with a possible, but not necessarily, list of peptide candidates that need to be experimentally confirmed for vaccine production. During the subsequent years, reverse vaccinology has dramatically changed: now it consists of a large number of bioinformatics tools and processes, namely subtractive proteomics, computational vaccinology, immunoinformatics, and in silico related procedures. However, the state of the art of reverse vaccinology still misses the ability to predict the efficacy of the proposed vaccine formulation. Here, we describe how to fill the gap by introducing an advanced immune system simulator that tests the efficacy of a vaccine formulation against the disease for which it has been designed. As a working example, we entirely apply this advanced reverse vaccinology approach to design and predict the efficacy of a potential vaccine formulation against influenza H5N1. Climate change and melting glaciers are critical due to reactivating frozen viruses and emerging new pandemics. H5N1 is one of the potential strains present in icy lakes that can raise a pandemic. Investigating structural antigen protein is the most profitable therapeutic pipeline to generate an effective vaccine against H5N1. In particular, we designed a multi-epitope vaccine based on predicted epitopes of hemagglutinin and neuraminidase proteins that potentially trigger B-cells, CD4, and CD8 T-cell immune responses. Antigenicity and toxicity of all predicted CTL, Helper T-lymphocytes, and B-cells epitopes were evaluated, and both antigenic and non-allergenic epitopes were selected. From the perspective of advanced reverse vaccinology, the Universal Immune System Simulator, an in silico trial computational framework, was applied to estimate vaccine efficacy using a cohort of 100 digital patients.https://doi.org/10.1186/s12859-023-05374-1In silico trialVaccine desigInfluenzaReverse vaccinologyUISS |
| spellingShingle | Giulia Russo Elena Crispino Avisa Maleki Valentina Di Salvatore Filippo Stanco Francesco Pappalardo Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza BMC Bioinformatics In silico trial Vaccine desig Influenza Reverse vaccinology UISS |
| title | Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza |
| title_full | Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza |
| title_fullStr | Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza |
| title_full_unstemmed | Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza |
| title_short | Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza |
| title_sort | beyond the state of the art of reverse vaccinology predicting vaccine efficacy with the universal immune system simulator for influenza |
| topic | In silico trial Vaccine desig Influenza Reverse vaccinology UISS |
| url | https://doi.org/10.1186/s12859-023-05374-1 |
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