Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design
In the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanom...
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MDPI AG
2023-05-01
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Online Access: | https://www.mdpi.com/1422-0067/24/10/9024 |
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author | Iker Malaina Lorena Gonzalez-Melero Luis Martínez Aiala Salvador Ana Sanchez-Diez Aintzane Asumendi Javier Margareto Jose Carrasco-Pujante Leire Legarreta María Asunción García Martín Blas Pérez-Pinilla Rosa Izu Ildefonso Martínez de la Fuente Manoli Igartua Santos Alonso Rosa Maria Hernandez María Dolores Boyano |
author_facet | Iker Malaina Lorena Gonzalez-Melero Luis Martínez Aiala Salvador Ana Sanchez-Diez Aintzane Asumendi Javier Margareto Jose Carrasco-Pujante Leire Legarreta María Asunción García Martín Blas Pérez-Pinilla Rosa Izu Ildefonso Martínez de la Fuente Manoli Igartua Santos Alonso Rosa Maria Hernandez María Dolores Boyano |
author_sort | Iker Malaina |
collection | DOAJ |
description | In the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanoma in different stages were obtained, resulting in a total of 6048 potential neoantigens gathered. Thereafter, the immunological responses generated by some of those neoantigens ex vivo were tested, using a vaccine designed by a new optimization approach and encapsulated in nanoparticles. Our bioinformatic analysis indicated that no differences were found between the number of neoantigens and that of non-mutated sequences detected as potential binders by IEDB tools. However, those tools were able to highlight neoantigens over non-mutated peptides in HLA-II recognition (<i>p</i>-value 0.03). However, neither HLA-I binding affinity (<i>p</i>-value 0.08) nor Class I immunogenicity values (<i>p</i>-value 0.96) indicated significant differences for the latter parameters. Subsequently, the new vaccine, using aggregative functions and combinatorial optimization, was designed. The six best neoantigens were selected and formulated into two nanoparticles, with which the immune response ex vivo was evaluated, demonstrating a specific activation of the immune response. This study reinforces the use of bioinformatic tools in vaccine development, as their usefulness is proven both in silico and ex vivo. |
first_indexed | 2024-03-11T03:38:46Z |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-11T03:38:46Z |
publishDate | 2023-05-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-9eda8a8c420d4e0ca9ec9566ae3f8edd2023-11-18T01:46:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410902410.3390/ijms24109024Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine DesignIker Malaina0Lorena Gonzalez-Melero1Luis Martínez2Aiala Salvador3Ana Sanchez-Diez4Aintzane Asumendi5Javier Margareto6Jose Carrasco-Pujante7Leire Legarreta8María Asunción García9Martín Blas Pérez-Pinilla10Rosa Izu11Ildefonso Martínez de la Fuente12Manoli Igartua13Santos Alonso14Rosa Maria Hernandez15María Dolores Boyano16Department of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainDepartment of Dermatology, Basurto University Hospital, 48013 Bilbao, SpainBiocruces Bizkaia Health Research Institute, 48903 Barakaldo, SpainTechnological Services Division, Health and Quality of Life, TECNALIA, 01510 Miñano, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainDepartment of Dermatology, Basurto University Hospital, 48013 Bilbao, SpainDepartment of Mathematics, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainDepartment of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, SpainNanoBioCel Research Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, SpainBiocruces Bizkaia Health Research Institute, 48903 Barakaldo, SpainIn the last few years, the importance of neoantigens in the development of personalized antitumor vaccines has increased remarkably. In order to study whether bioinformatic tools are effective in detecting neoantigens that generate an immune response, DNA samples from patients with cutaneous melanoma in different stages were obtained, resulting in a total of 6048 potential neoantigens gathered. Thereafter, the immunological responses generated by some of those neoantigens ex vivo were tested, using a vaccine designed by a new optimization approach and encapsulated in nanoparticles. Our bioinformatic analysis indicated that no differences were found between the number of neoantigens and that of non-mutated sequences detected as potential binders by IEDB tools. However, those tools were able to highlight neoantigens over non-mutated peptides in HLA-II recognition (<i>p</i>-value 0.03). However, neither HLA-I binding affinity (<i>p</i>-value 0.08) nor Class I immunogenicity values (<i>p</i>-value 0.96) indicated significant differences for the latter parameters. Subsequently, the new vaccine, using aggregative functions and combinatorial optimization, was designed. The six best neoantigens were selected and formulated into two nanoparticles, with which the immune response ex vivo was evaluated, demonstrating a specific activation of the immune response. This study reinforces the use of bioinformatic tools in vaccine development, as their usefulness is proven both in silico and ex vivo.https://www.mdpi.com/1422-0067/24/10/9024bioinformaticsex vivohuman leucocytic antigenimmunogenicitynanoparticleneoantigen |
spellingShingle | Iker Malaina Lorena Gonzalez-Melero Luis Martínez Aiala Salvador Ana Sanchez-Diez Aintzane Asumendi Javier Margareto Jose Carrasco-Pujante Leire Legarreta María Asunción García Martín Blas Pérez-Pinilla Rosa Izu Ildefonso Martínez de la Fuente Manoli Igartua Santos Alonso Rosa Maria Hernandez María Dolores Boyano Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design International Journal of Molecular Sciences bioinformatics ex vivo human leucocytic antigen immunogenicity nanoparticle neoantigen |
title | Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design |
title_full | Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design |
title_fullStr | Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design |
title_full_unstemmed | Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design |
title_short | Computational and Experimental Evaluation of the Immune Response of Neoantigens for Personalized Vaccine Design |
title_sort | computational and experimental evaluation of the immune response of neoantigens for personalized vaccine design |
topic | bioinformatics ex vivo human leucocytic antigen immunogenicity nanoparticle neoantigen |
url | https://www.mdpi.com/1422-0067/24/10/9024 |
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